Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis

Over the past three-decades, Janus kinase (Jak) and signal transducer and activator of transcription (STAT) signaling has emerged as a paradigm to understand the involvement of signal transduction in development and disease pathology. At the molecular level, cytokines and interleukins steer Jak/STAT signaling to transcriptional regulation of target genes, which are involved in cell differentiation, migration, and proliferation. Jak/STAT signaling is involved in various types of blood cell disorders and cancers in humans, and its activation is associated with carcinomas that are more invasive or likely to become metastatic. Despite immense information regarding Jak/STAT regulation, the signaling network has numerous missing links, which is slowing the progress towards developing drug therapies. In mammals, many components act in this cascade, with substantial cross-talk with other signaling pathways. In Drosophila, there are fewer pathway components, which has enabled significant discoveries regarding well-conserved regulatory mechanisms. Work across species illustrates the relevance of these regulators in humans. In this review, we showcase fundamental Jak/STAT regulation mechanisms in blood cells, stem cells, and cell motility. We examine the functional relevance of key conserved regulators from Drosophila to human cancer stem cells and metastasis. Finally, we spotlight less characterized regulators of Drosophila Jak/STAT signaling, which stand as promising candidates to be investigated in cancer biology. These comparisons illustrate the value of using Drosophila as a model for uncovering the roles of Jak/STAT signaling and the molecular means by which the pathway is controlled.

[1]  T. Graeber,et al.  Primary Resistance to PD-1 Blockade Mediated by JAK1/2 Mutations. , 2017, Cancer discovery.

[2]  Patterning: JAK-STAT Signalling in the Drosophila Follicular Epithelium , 2003, Current Biology.

[3]  M. Fang,et al.  The prognostic significance of bromodomain PHD-finger transcription factor in colorectal carcinoma and association with vimentin and E-cadherin , 2015, Journal of Cancer Research and Clinical Oncology.

[4]  J. Darnell,et al.  A Drosophila PIAS homologue negatively regulates stat92E , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Stephen Brown,et al.  Identification of the first invertebrate interleukin JAK/STAT receptor, the Drosophila gene domeless , 2001, Current Biology.

[6]  Nicola Gebbia,et al.  STAT proteins: From normal control of cellular events to tumorigenesis , 2003, Journal of cellular physiology.

[7]  Courtney R. Plumlee,et al.  Inteferons pen the JAK-STAT pathway. , 2008, Seminars in cell & developmental biology.

[8]  L. Latonen,et al.  Amplification of the 9p13.3 chromosomal region in prostate cancer , 2016, Genes, chromosomes & cancer.

[9]  P. Marynen,et al.  Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia. , 1997, Blood.

[10]  Norbert Perrimon,et al.  Signaling role of hemocytes in Drosophila JAK/STAT-dependent response to septic injury. , 2003, Developmental cell.

[11]  H. Ford,et al.  Eya2 Is Required to Mediate the Pro-Metastatic Functions of Six1 Via the Induction of TGF-β Signaling, Epithelial-Mesenchymal Transition, and Cancer Stem Cell Properties , 2011, Oncogene.

[12]  J. Darnell,et al.  The role of STATs in transcriptional control and their impact on cellular function , 2000, Oncogene.

[13]  G. Stark,et al.  Roles of unphosphorylated STATs in signaling , 2008, Cell Research.

[14]  Norbert Perrimon,et al.  Genome-wide RNAi analysis of JAK/STAT signaling components in Drosophila. , 2005, Genes & development.

[15]  R. Lucito,et al.  Protein-tyrosine Phosphatase 1B Antagonized Signaling by Insulin-like Growth Factor-1 Receptor and Kinase BRK/PTK6 in Ovarian Cancer Cells*♦ , 2013, The Journal of Biological Chemistry.

[16]  Shizuo Akira,et al.  Functional Roles of STAT Family Proteins: Lessons from Knockout Mice , 1999, Stem cells.

[17]  M. Meister,et al.  Control of blood cell homeostasis in Drosophila larvae by the posterior signalling centre , 2007, Nature.

[18]  Zhengyang Guo,et al.  Comprehensive profiling of novel microRNA-9 targets and a tumor suppressor role of microRNA-9 via targeting IGF2BP1 in hepatocellular carcinoma , 2015, Oncotarget.

[19]  W. Orr,et al.  The effect of peroxiredoxin 4 on fly physiology is a complex interplay of antioxidant and signaling functions , 2013, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[20]  Y. S. Park,et al.  Peroxiredoxin 4 as an independent prognostic marker for survival in patients with early-stage lung squamous cell carcinoma. , 2015, International journal of clinical and experimental pathology.

[21]  A. Shilatifard,et al.  Histone demethylase dUTX antagonizes JAK-STAT signaling to maintain proper gene expression and architecture of the Drosophila testis niche , 2013, Development.

[22]  T. Roberts,et al.  Mutation in the Jak kinase JH2 domain hyperactivates Drosophila and mammalian Jak-Stat pathways , 1997, Molecular and cellular biology.

[23]  M. Fang,et al.  BPTF Associated with EMT Indicates Negative Prognosis in Patients with Hepatocellular Carcinoma , 2015, Digestive Diseases and Sciences.

[24]  Yu Qin,et al.  BPTF promotes tumor growth and predicts poor prognosis in lung adenocarcinomas , 2015, Oncotarget.

[25]  C. Dubois,et al.  Attenuation of MET-mediated migration and invasion in hepatocellular carcinoma cells by SOCS1 , 2017, World journal of gastroenterology.

[26]  Willis X. Li,et al.  Patterns and functions of STAT activation during Drosophila embryogenesis , 2003, Mechanisms of Development.

[27]  A. Yoshimura,et al.  CIS, a cytokine inducible SH2 protein, is a target of the JAK-STAT5 pathway and modulates STAT5 activation. , 1997, Blood.

[28]  J. Darnell,et al.  Signalling: STATs: transcriptional control and biological impact , 2002, Nature Reviews Molecular Cell Biology.

[29]  S. Constantinescu,et al.  JAK1 and Tyk2 Activation by the Homologous Polycythemia Vera JAK2 V617F Mutation , 2005, Journal of Biological Chemistry.

[30]  M. Koch,et al.  Expressional STAT3/STAT5 Ratio is an Independent Prognostic Marker in Colon Carcinoma , 2015, Annals of Surgical Oncology.

[31]  B. Mathey-Prevot,et al.  SOCS36E, a novel Drosophila SOCS protein, suppresses JAK/STAT and EGF-R signalling in the imaginal wing disc , 2002, Oncogene.

[32]  Shanshan Guo,et al.  Clinicopathological significance of overexpression of interleukin-6 in colorectal cancer , 2017, World journal of gastroenterology.

[33]  Amy R. Peck,et al.  PTP1B suppresses prolactin activation of Stat5 in breast cancer cells. , 2010, The American journal of pathology.

[34]  Takaho A. Endo,et al.  A new protein containing an SH2 domain that inhibits JAK kinases , 1997, Nature.

[35]  Ming Li,et al.  The IL-6/JAK/Stat3 feed-forward loop drives tumorigenesis and metastasis. , 2013, Neoplasia.

[36]  D. Montell,et al.  Eyes Absent, a key repressor of polar cell fate during Drosophila oogenesis , 2002, Development.

[37]  J. Becker,et al.  STAT5 Contributes to Interferon Resistance of Melanoma Cells , 2005, Current Biology.

[38]  D. Harrison,et al.  Pleiotropy of the Drosophila JAK pathway cytokine Unpaired 3 in development and aging. , 2014, Developmental biology.

[39]  U. Banerjee,et al.  Genetic manipulation of AML1-ETO-induced expansion of hematopoietic precursors in a Drosophila model. , 2010, Blood.

[40]  Yuze Chen,et al.  miR-885-5p upregulation promotes colorectal cancer cell proliferation and migration by targeting suppressor of cytokine signaling , 2018, Oncology letters.

[41]  H. Meinhardt,et al.  Interpretation of the UPD/JAK/STAT morphogen gradient in Drosophila follicle cells , 2009, Cell cycle.

[42]  M. Zeidler,et al.  Ken & Barbie Selectively Regulates the Expression of a Subset of JAK/STAT Pathway Target Genes , 2006, Current Biology.

[43]  Kearney T. W. Gunsalus,et al.  Induction of the RNA regulator LIN28A is required for the growth and pathogenesis of RESTless breast tumors. , 2012, Cancer research.

[44]  M. Starz-Gaiano,et al.  Circuitous Genetic Regulation Governs a Straightforward Cell Migration. , 2016, Trends in genetics : TIG.

[45]  Jiaqi Liu,et al.  HDAC6 interacts with PTPN1 to enhance melanoma cells progression. , 2018, Biochemical and biophysical research communications.

[46]  J. Leatherman,et al.  Zfh-1 controls somatic stem cell self-renewal in the Drosophila testis and nonautonomously influences germline stem cell self-renewal. , 2008, Cell stem cell.

[47]  P. Lin,et al.  C/EBP-δ regulates VEGF-C autocrine signaling in lymphangiogenesis and metastasis of lung cancer through HIF-1α , 2011, Oncogene.

[48]  C. Dearolf.  Fruit fly "leukemia". , 1998, Biochimica et biophysica acta.

[49]  L. Hennighausen,et al.  Interpretation of cytokine signaling through the transcription factors STAT5A and STAT5B. , 2008, Genes & development.

[50]  Y. Hegerfeldt,et al.  Collective cell movement in primary melanoma explants: plasticity of cell-cell interaction, beta1-integrin function, and migration strategies. , 2002, Cancer research.

[51]  Byung Hak Kim,et al.  A small-molecule compound identified through a cell-based screening inhibits JAK/STAT pathway signaling in human cancer cells , 2008, Molecular Cancer Therapeutics.

[52]  T. Toyama,et al.  Naturally occurring dominant-negative Stat5 suppresses transcriptional activity of estrogen receptors and induces apoptosis in T47D breast cancer cells , 2003, Oncogene.

[53]  D. Hilton,et al.  SOCS: physiological suppressors of cytokine signaling. , 2000, Journal of cell science.

[54]  J. C. Hombría,et al.  JAK-STAT pathway in Drosophila morphogenesis , 2013, JAK-STAT.

[55]  Rong-peng Dong,et al.  MicroRNA-150 functions as a tumor suppressor in osteosarcoma by targeting IGF2BP1 , 2016, Tumor Biology.

[56]  Xinhua Lin,et al.  Windpipe Controls Drosophila Intestinal Homeostasis by Regulating JAK/STAT Pathway via Promoting Receptor Endocytosis and Lysosomal Degradation , 2015, PLoS genetics.

[57]  M. Van Doren,et al.  Jak-STAT regulation of male germline stem cell establishment during Drosophila embryogenesis. , 2009, Developmental biology.

[58]  H. Luo,et al.  The Drosophila Jak kinase hopscotch is required for multiple developmental processes in the eye. , 1999, Developmental biology.

[59]  Y. H. Sun,et al.  Long‐range effect of upd, a ligand for Jak/STAT pathway, on cell cycle in Drosophila eye development , 2004, Genesis.

[60]  E. Matunis,et al.  JAK-STAT Signal Inhibition Regulates Competition in the Drosophila Testis Stem Cell Niche , 2009, Science.

[61]  J. Palvimo,et al.  PIAS proteins: pleiotropic interactors associated with SUMO , 2009, Cellular and Molecular Life Sciences.

[62]  Nunzio Bottini,et al.  Protein tyrosine phosphatases and the immune response , 2005, Nature Reviews Immunology.

[63]  Guillaume Valentin,et al.  A systematic analysis of Tinman function reveals Eya and JAK-STAT signaling as essential regulators of muscle development. , 2009, Developmental cell.

[64]  Robert A. Smith,et al.  Translational potential of cancer stem cells: A review of the detection of cancer stem cells and their roles in cancer recurrence and cancer treatment. , 2015, Experimental cell research.

[65]  P. Friedl,et al.  Collective cell migration in morphogenesis, regeneration and cancer , 2009, Nature Reviews Molecular Cell Biology.

[66]  Amanda J. Monahan,et al.  Socs36E attenuates STAT signaling to optimize motile cell specification in the Drosophila ovary. , 2013, Developmental biology.

[67]  Yvonne Tay,et al.  A novel SOCS5/miR‐18/miR‐25 axis promotes tumorigenesis in liver cancer , 2018, International Journal of Cancer.

[68]  T. Tokusumi,et al.  The Friend of GATA protein U-shaped functions as a hematopoietic tumor suppressor in Drosophila. , 2007, Developmental biology.

[69]  A. Yoshimura,et al.  The Jak-Stat pathway in normal and perturbed hematopoiesis. , 2000, Blood.

[70]  Xufeng Zhang,et al.  MicroRNA-98-5p Inhibits Cell Proliferation and Induces Cell Apoptosis in Hepatocellular Carcinoma via Targeting IGF2BP1 , 2017, Oncology research.

[71]  J. Casanova,et al.  Inborn errors of human JAKs and STATs. , 2012, Immunity.

[72]  Kozo Nakamura,et al.  Overexpression of the csk gene suppresses tumor metastasis in vivo , 2000, International journal of cancer.

[73]  M. Meister,et al.  A Short Receptor Downregulates JAK/STAT Signalling to Control the Drosophila Cellular Immune Response , 2010, PLoS biology.

[74]  M. Amoyel,et al.  Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis , 2016, PLoS genetics.

[75]  N. Perrimon,et al.  Drosophila unpaired encodes a secreted protein that activates the JAK signaling pathway. , 1998, Genes & development.

[76]  J. Xiong,et al.  MicroRNA-140-5p targets insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress cervical cancer growth and metastasis , 2016, Oncotarget.

[77]  D. Harrison,et al.  A gradient of JAK pathway activity patterns the anterior-posterior axis of the follicular epithelium. , 2003, Developmental cell.

[78]  Stephen Brown,et al.  Advances in genome-wide RNAi cellular screens: a case study using the Drosophila JAK/STAT pathway , 2012, BMC Genomics.

[79]  G. Sethi,et al.  Nanoparticles Targeting STATs in Cancer Therapy , 2019, Cells.

[80]  D. Levy,et al.  Divergent roles of STAT1 and STAT5 in malignancy as revealed by gene disruptions in mice , 2000, Oncogene.

[81]  P. Schwille,et al.  Essential role of endocytosis for interleukin-4-receptor-mediated JAK/STAT signalling , 2015, Journal of Cell Science.

[82]  P. Murray.  The JAK-STAT Signaling Pathway: Input and Output Integration1 , 2007, The Journal of Immunology.

[83]  D. Montell,et al.  Requirement for Par-6 and Bazooka in Drosophila border cell migration , 2004, Development.

[84]  Norbert Perrimon,et al.  marelle Acts Downstream of the Drosophila HOP/JAK Kinase and Encodes a Protein Similar to the Mammalian STATs , 1996, Cell.

[85]  A. Ciechanover,et al.  The ubiquitin conjugation system is required for ligand‐induced endocytosis and degradation of the growth hormone receptor. , 1996, The EMBO journal.

[86]  S. DiNardo,et al.  A somatic role for eyes absent (eya) and sine oculis (so) in Drosophila spermatocyte development. , 2003, Developmental biology.

[87]  W. Stec,et al.  Mechanisms of JAK/STAT pathway negative regulation by the short coreceptor Eye Transformer/Latran , 2016, Molecular biology of the cell.

[88]  Qian Qian,et al.  SOCS1 is associated with clinical progression and acts as an oncogenic role in triple‐negative breast cancer , 2018, IUBMB life.

[89]  M. Inamdar,et al.  Asrij Maintains the Stem Cell Niche and Controls Differentiation during Drosophila Lymph Gland Hematopoiesis , 2011, PloS one.

[90]  S. Nada,et al.  Csk defines the ability of integrin-mediated cell adhesion and migration in human colon cancer cells: implication for a potential role in cancer metastasis , 2004, Oncogene.

[91]  W. Vainchenker,et al.  JAK2, the JAK2 V617F mutant and cytokine receptors. , 2007, Pathologie-biologie.

[92]  K. Dorritie,et al.  STAT transcription factors in normal and cancer stem cells. , 2014, Advances in biological regulation.

[93]  Z. Jia,et al.  Differential expression of peroxiredoxins in prostate cancer: Consistent upregulation of PRDX3 and PRDX4 , 2011, The Prostate.

[94]  Q. Zhan,et al.  PTP1B Contributes to Calreticulin-Induced Metastatic Phenotypes in Esophageal Squamous Cell Carcinoma , 2013, Molecular Cancer Research.

[95]  Yun-jie Wang,et al.  Eya2 overexpression promotes the invasion of human astrocytoma through the regulation of ERK/MMP9 signaling , 2017, International journal of molecular medicine.

[96]  J. Hong,et al.  4-parvifuran inhibits metastatic and invasive actions through the JAK2/STAT3 pathway in osteosarcoma cells , 2017, Archives of Pharmacal Research.

[97]  Hans Meinhardt,et al.  Feedback inhibition of Jak/STAT signaling by apontic is required to limit an invasive cell population. , 2008, Developmental cell.

[98]  Achim Krüger,et al.  Systemic Ablation of MMP-9 Triggers Invasive Growth and Metastasis of Pancreatic Cancer via Deregulation of IL6 Expression in the Bone Marrow , 2016, Molecular Cancer Research.

[99]  Seong-Jin Kim,et al.  Dysregulated JAK2 expression by TrkC promotes metastasis potential, and EMT program of metastatic breast cancer , 2016, Scientific Reports.

[100]  Stephen Brown,et al.  Characterisation of Upd2, a Drosophila JAK/STAT pathway ligand. , 2005, Developmental biology.

[101]  U. Tepass,et al.  DE-Cadherin Is Required for Intercellular Motility during Drosophila Oogenesis , 1999, The Journal of cell biology.

[102]  D. Harrison,et al.  Two Drosophila suppressors of cytokine signaling (SOCS) differentially regulate JAK and EGFR pathway activities , 2004, BMC Cell Biology.

[103]  M. Amoyel,et al.  Functions of the Drosophila JAK-STAT pathway , 2012, JAK-STAT.

[104]  W. P. Hanratty,et al.  The Drosophila Tumorous lethal hematopoietic oncogene is a dominant mutation in the hopscotch locus , 1993, Molecular and General Genetics MGG.

[105]  L. Travassos,et al.  Role of SOCS-1 Gene on Melanoma Cell Growth and Tumor Development. , 2011, Translational oncology.

[106]  Stephen Brown,et al.  Methotrexate Is a JAK/STAT Pathway Inhibitor , 2015, PloS one.

[107]  J. Duhart,et al.  The repertoire of epithelial morphogenesis on display: Progressive elaboration of Drosophila egg structure , 2017, Mechanisms of Development.

[108]  E. Matunis,et al.  Novel regulators revealed by profiling Drosophila testis stem cells within their niche. , 2006, Developmental biology.

[109]  T. Jiang,et al.  STAT5 regulates glioma cell invasion by pathways dependent and independent of STAT5 DNA binding , 2011, Neuroscience Letters.

[110]  W. Kim,et al.  The combination of methylsulfonylmethane and tamoxifen inhibits the Jak2/STAT5b pathway and synergistically inhibits tumor growth and metastasis in ER-positive breast cancer xenografts , 2015, BMC Cancer.

[111]  Norbert Perrimon,et al.  Parallel Chemical Genetic and Genome-Wide RNAi Screens Identify Cytokinesis Inhibitors and Targets , 2004, PLoS biology.

[112]  S. Cohen,et al.  Oncogenic cooperation between SOCS family proteins and EGFR identified using a Drosophila epithelial transformation model. , 2012, Genes & development.

[113]  Z. Culig,et al.  Interleukin-6 trans-signalling differentially regulates proliferation, migration, adhesion and maspin expression in human prostate cancer cells , 2010, Endocrine-related cancer.

[114]  A. Aguzzi,et al.  Endothelial CCR2 signaling induced by colon carcinoma cells enables extravasation via the JAK2-Stat5 and p38MAPK pathway. , 2012, Cancer cell.

[115]  A. Spradling,et al.  slow border cells, a locus required for a developmentally regulated cell migration during oogenesis, encodes Drosophila C EBP , 1992, Cell.

[116]  P. Bradley,et al.  Organ positioning in Drosophila requires complex tissue-tissue interactions. , 2005, Developmental biology.

[117]  E. Matunis,et al.  Somatic control of germline sexual development is mediated by the JAK/STAT pathway , 2005, Nature.

[118]  T. Cline,et al.  An extracellular activator of the Drosophila JAK/STAT pathway is a sex-determination signal element , 2000, Nature.

[119]  E. Vellenga,et al.  STAT5-mediated self-renewal of normal hematopoietic and leukemic stem cells , 2012, JAK-STAT.

[120]  M. Kraus,et al.  Characterization of a Stat-like DNA Binding Activity in Drosophila melanogaster(*) , 1995, The Journal of Biological Chemistry.

[121]  H. Rui,et al.  Prolactin inhibits BCL6 expression in breast cancer through a Stat5a-dependent mechanism. , 2010, Cancer research.

[122]  H. Luo,et al.  An amino acid substitution in the Drosophila hopTum‐l Jak kinase causes leukemia‐like hematopoietic defects. , 1995, The EMBO journal.

[123]  B. Leiby,et al.  Stat5 promotes metastatic behavior of human prostate cancer cells in vitro and in vivo. , 2010, Endocrine-related cancer.

[124]  Claude Desplan,et al.  Identification of a Stat Gene That Functions in Drosophila Development , 1996, Cell.

[125]  C. Cherry,et al.  Epigenetic regulation of stem cell maintenance in the Drosophila testis via the nucleosome-remodeling factor NURF. , 2010, Cell stem cell.

[126]  Yusuke Nakamura,et al.  Increased Expression of Insulin-like Growth Factor-II Messenger RNA–Binding Protein 1 Is Associated with Tumor Progression in Patients with Lung Cancer , 2007, Clinical Cancer Research.

[127]  Hua Yu,et al.  Revisiting STAT3 signalling in cancer: new and unexpected biological functions , 2014, Nature Reviews Cancer.

[128]  E. Hafen,et al.  SOCS36E specifically interferes with Sevenless signaling during Drosophila eye development. , 2009, Developmental biology.

[129]  W. Alexander,et al.  The role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune response. , 2004, Annual review of immunology.

[130]  D. St Johnston,et al.  A repeated IMP-binding motif controls oskar mRNA translation and anchoring independently of Drosophila melanogaster IMP , 2006, The Journal of cell biology.

[131]  N. Perrimon,et al.  Systematic screen of chemotherapeutics in Drosophila stem cell tumors , 2014, Proceedings of the National Academy of Sciences.

[132]  M. Zeidler,et al.  The Drosophila JAK-STAT pathway , 2013, JAK-STAT.

[133]  Amanda J. Monahan,et al.  Apontic regulates somatic stem cell numbers in Drosophila testes , 2016, BMC Developmental Biology.

[134]  S. Noselli,et al.  Dynamics of the basement membrane in invasive epithelial clusters in Drosophila , 2005, Development.

[135]  M. Kubo,et al.  Suppression of STAT5 Functions in Liver, Mammary Glands, and T Cells in Cytokine-Inducible SH2-Containing Protein 1 Transgenic Mice , 1999, Molecular and Cellular Biology.

[136]  Stephen Brown,et al.  Effect of methotrexate on JAK/STAT pathway activation in myeloproliferative neoplasms , 2015, The Lancet.

[137]  I. Campbell.  Cytokine-mediated inflammation, tumorigenesis, and disease-associated JAK/STAT/SOCS signaling circuits in the CNS , 2005, Brain Research Reviews.

[138]  Yongdong Feng,et al.  Human colorectal cancer-derived mesenchymal stem cells promote colorectal cancer progression through IL-6/JAK2/STAT3 signaling , 2018, Cell Death & Disease.

[139]  Saikat Ghosh,et al.  Active Hematopoietic Hubs in Drosophila Adults Generate Hemocytes and Contribute to Immune Response , 2015, Developmental cell.

[140]  E. Matunis,et al.  Control of Stem Cell Self-Renewal in Drosophila Spermatogenesis by JAK-STAT Signaling , 2001, Science.

[141]  J. Xie,et al.  BCL6 induces EMT by promoting the ZEB1-mediated transcription repression of E-cadherin in breast cancer cells. , 2015, Cancer letters.

[142]  R. Steward,et al.  JAK/STAT and the GATA factor Pannier control hemocyte maturation and differentiation in Drosophila. , 2011, Developmental biology.

[143]  M. Starz-Gaiano,et al.  Identification of Novel Regulators of the JAK/STAT Signaling Pathway that Control Border Cell Migration in the Drosophila Ovary , 2016, G3: Genes, Genomes, Genetics.

[144]  T. Zoranovic,et al.  Regulation of proliferation, cell competition, and cellular growth by the Drosophila JAK-STAT pathway , 2013, JAK-STAT.

[145]  S. Liyanarachchi,et al.  Suppression of Peroxiredoxin 4 in Glioblastoma Cells Increases Apoptosis and Reduces Tumor Growth , 2012, PloS one.

[146]  G. Juhász,et al.  Stem-cell-specific endocytic degradation defects lead to intestinal dysplasia in Drosophila , 2016, Disease Models & Mechanisms.

[147]  P. Dessen,et al.  Suppressor of cytokine signaling 1 modulates invasion and metastatic potential of colorectal cancer cells , 2014, Molecular oncology.

[148]  Leena-Maija Vanha-aho,et al.  Eye transformer is a negative regulator of Drosophila JAK/STAT signaling , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[149]  Z. Estrov,et al.  WP-1034, a novel JAK-STAT inhibitor, with proapoptotic and antileukemic activity in acute myeloid leukemia (AML). , 2005, Anticancer research.

[150]  G. Baeg,et al.  JAK/STAT signaling promotes regional specification by negatively regulating wingless expression in Drosophila , 2006, Development.

[151]  C. Piyathilake,et al.  Triple Negative Breast Cancer – An Overview , 2012, Hereditary genetics : current research.

[152]  Xiaobo Wang,et al.  aPKC is a key polarity determinant in coordinating the function of three distinct cell polarities during collective migration , 2018, Development.

[153]  A. Vincent,et al.  The Drosophila JAK-STAT pathway in blood cell formation and immunity , 2013, JAK-STAT.

[154]  P. Bult,et al.  Collective invasion in ductal and lobular breast cancer associates with distant metastasis , 2017, Clinical & Experimental Metastasis.

[155]  A. Nagel,et al.  The Putzig-NURF Nucleosome Remodeling Complex Is Required for Ecdysone Receptor Signaling and Innate Immunity in Drosophila melanogaster , 2011, Genetics.

[156]  So Yeon Kwon,et al.  Alternative Splicing of NURF301 Generates Distinct NURF Chromatin Remodeling Complexes with Altered Modified Histone Binding Specificities , 2009, PLoS genetics.

[157]  D. Montell,et al.  Ovarian Cancer Metastasis: Integrating insights from disparate model organisms , 2005, Nature Reviews Cancer.

[158]  C. Ghiglione,et al.  The endocytic control of JAK/STAT signalling in Drosophila , 2007, Journal of Cell Science.

[159]  A. Levitzki,et al.  Inhibition of acute lymphoblastic leukaemia by a Jak-2 inhibitor , 1996, Nature.

[160]  Hyeong-Kyu Lee,et al.  MS‐1020 is a novel small molecule that selectively inhibits JAK3 activity , 2010, British journal of haematology.

[161]  Jian-bo Zhang,et al.  IL-37b suppresses epithelial mesenchymal transition in hepatocellular carcinoma by inhibiting IL-6/STAT3 signaling. , 2018, Hepatobiliary & pancreatic diseases international : HBPD INT.

[162]  F. Jirik,et al.  A novel role for the SUMO E3 ligase PIAS1 in cancer metastasis , 2014, Oncoscience.

[163]  M. Milán,et al.  JAK/STAT controls organ size and fate specification by regulating morphogen production and signalling , 2017, Nature Communications.

[164]  L. Meng,et al.  SOX12 upregulation is associated with metastasis of hepatocellular carcinoma and increases CDK4 and IGF2BP1 expression. , 2017, European review for medical and pharmacological sciences.

[165]  N. Perrimon,et al.  The roles of the Drosophila JAK/STAT pathway , 2000, Oncogene.

[166]  F. Wang,et al.  IL‐7–Mediated IL‐7R‐JAK3/STAT5 signalling pathway contributes to chemotherapeutic sensitivity in non–small‐cell lung cancer , 2019, Cell proliferation.

[167]  A. Bashirullah,et al.  Genetic Control of Specificity to Steroid-Triggered Responses in Drosophila , 2013, Genetics.

[168]  A. Pret,et al.  JAK/STAT autocontrol of ligand-producing cell number through apoptosis , 2013, Development.

[169]  Fabrice Carballès,et al.  The Drosophila cytokine receptor Domeless controls border cell migration and epithelial polarization during oogenesis , 2002, Development.

[170]  L. Soroceanu,et al.  The Role of BPTF in Melanoma Progression and in Response to BRAF-Targeted Therapy , 2015, Journal of the National Cancer Institute.

[171]  E. Levine,et al.  The let-7–Imp axis regulates ageing of the Drosophila testis stem-cell niche , 2012, Nature.

[172]  C. Janeway,et al.  PVF2, a PDGF/VEGF‐like growth factor, induces hemocyte proliferation in Drosophila larvae , 2002, EMBO reports.

[173]  J. O’Shea,et al.  Cytokine signaling modules in inflammatory responses. , 2008, Immunity.

[174]  Bo Liu,et al.  Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis , 2018, Genes & diseases.

[175]  Willis X Li,et al.  JAK-STAT in heterochromatin and genome stability , 2013, JAK-STAT.

[176]  M. Gaestel,et al.  Cross-regulation of cytokine signalling: pro-inflammatory cytokines restrict IL-6 signalling through receptor internalisation and degradation , 2010, Journal of Cell Science.

[177]  M. Zeidler,et al.  Transcriptional targets of Drosophila JAK/STAT pathway signalling as effectors of haematopoietic tumour formation , 2010, EMBO reports.

[178]  Michael Boutros,et al.  Identification of JAK/STAT signalling components by genome-wide RNA interference , 2005, Nature.

[179]  I. Rebay,et al.  Interactions with the Abelson tyrosine kinase reveal compartmentalization of eyes absent function between nucleus and cytoplasm. , 2009, Developmental cell.

[180]  D. Montell,et al.  Lessons from border cell migration in the Drosophila ovary: A role for myosin VI in dissemination of human ovarian cancer. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[181]  G. Mardon,et al.  Eyes absent represents a class of protein tyrosine phosphatases , 2003, Nature.

[182]  H. Meinhardt,et al.  miRNA-mediated feedback inhibition of JAK/STAT morphogen signaling establishes a cell fate threshold , 2011, Nature Cell Biology.

[183]  E. Smythe,et al.  Differential activities of the Drosophila JAK/STAT pathway ligands Upd, Upd2 and Upd3. , 2011, Cellular signalling.

[184]  Yingyong Hou,et al.  Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis , 2018, Nature Communications.

[185]  Valesca Anschau,et al.  Dissecting Major Signaling Pathways throughout the Development of Prostate Cancer , 2013, Prostate cancer.

[186]  Lynette M. Smith,et al.  Carboxyl-terminal domain of MUC16 imparts tumorigenic and metastatic functions through nuclear translocation of JAK2 to pancreatic cancer cells , 2015, Oncotarget.

[187]  E. Bach,et al.  A Genetic Screen Reveals an Unexpected Role for Yorkie Signaling in JAK/STAT-Dependent Hematopoietic Malignancies in Drosophila melanogaster , 2017, G3: Genes, Genomes, Genetics.

[188]  Zhen Shi,et al.  Enhancer of polycomb coordinates multiple signaling pathways to promote both cyst and germline stem cell differentiation in the Drosophila adult testis , 2017, PLoS genetics.

[189]  A. Maitra,et al.  Epigenetic silencing of EYA2 in pancreatic adenocarcinomas promotes tumor growth , 2014, Oncotarget.

[190]  Pierre B. Cattenoz,et al.  Embryonic hematopoiesis modulates the inflammatory response and larval hematopoiesis in Drosophila , 2018, eLife.

[191]  Jianfeng Cai,et al.  Berberine Inhibits Invasion and Metastasis of Colorectal Cancer Cells via COX-2/PGE2 Mediated JAK2/STAT3 Signaling Pathway , 2015, PloS one.

[192]  C. Desplan,et al.  Power tools for gene expression and clonal analysis in Drosophila , 2011, Nature Methods.

[193]  H. Herranz,et al.  Yorkie and JNK Control Tumorigenesis in Drosophila Cells with Cytokinesis Failure. , 2018, Cell reports.

[194]  B. Dréno,et al.  Loss of oncostatin M receptor β in metastatic melanoma cells , 2007, Oncogene.

[195]  A. Polpitiya,et al.  The Drosophila melanogaster sperm proteome-II (DmSP-II). , 2010, Journal of proteomics.

[196]  L. Dobens,et al.  The Drosophila STAT protein, stat92E, regulates follicle cell differentiation during oogenesis. , 2002, Developmental biology.

[197]  R. Steward,et al.  Melanotic Mutants in Drosophila: Pathways and Phenotypes , 2006, Genetics.

[198]  Y. Li,et al.  The EGFR/miR-338-3p/EYA2 axis controls breast tumor growth and lung metastasis , 2017, Cell Death & Disease.

[199]  C. Xiao,et al.  Aberrant hypomethylation and overexpression of the eyes absent homologue 2 suppresses tumor cell growth of human lung adenocarcinoma cells. , 2015, Oncology reports.

[200]  S. Noselli,et al.  Asymmetric localisation of cytokine mRNA is essential for JAK/STAT activation during cell invasiveness , 2011, Development.

[201]  Gaudenz Danuser,et al.  Mechanical Feedback through E-Cadherin Promotes Direction Sensing during Collective Cell Migration , 2014, Cell.

[202]  Overexpression of PTP1B in human colorectal cancer and its association with tumor progression and prognosis , 2014, Journal of Molecular Histology.

[203]  N. Fossett.  Signal transduction pathways, intrinsic regulators, and the control of cell fate choice. , 2013, Biochimica et biophysica acta.

[204]  Mehdi Nosrati,et al.  Pleckstrin homology domain-interacting protein (PHIP) as a marker and mediator of melanoma metastasis , 2012, Proceedings of the National Academy of Sciences.

[205]  N. Perrimon,et al.  l(1)hopscotch, A larval-pupal zygotic lethal with a specific maternal effect on segmentation in Drosophila. , 1986, Developmental biology.

[206]  Xianquan Zhang,et al.  IL6-induced metastasis modulators p-STAT3, MMP-2 and MMP-9 are targets of 3,3′-diindolylmethane in ovarian cancer cells , 2015, Cellular Oncology.

[207]  M. Zeidler,et al.  JAK/STAT signalling in Drosophila: insights into conserved regulatory and cellular functions , 2006, Development.

[208]  C. Roehrborn,et al.  Soluble gp130 regulates prostate cancer invasion and progression in an interleukin-6 dependent and independent manner. , 2011, The Journal of urology.

[209]  W. Stec,et al.  Negative regulation of Drosophila JAK–STAT signalling by endocytic trafficking , 2010, Journal of Cell Science.

[210]  L. Hsu,et al.  CCAAT/Enhancer Binding Protein δ in Macrophages Contributes to Immunosuppression and Inhibits Phagocytosis in Nasopharyngeal Carcinoma , 2013, Science Signaling.

[211]  N. Bausek.  JAK-STAT signaling in stem cells and their niches in Drosophila , 2013, JAK-STAT.

[212]  N. Perrimon,et al.  The PDGF/VEGF receptor controls blood cell survival in Drosophila. , 2004, Developmental cell.

[213]  Shengrong Sun,et al.  Protein tyrosine phosphatase 1B expression contributes to the development of breast cancer , 2017, Journal of Zhejiang University-SCIENCE B.

[214]  Willis X. Li,et al.  Coactivation of STAT and Ras is required for germ cell proliferation and invasive migration in Drosophila. , 2003, Developmental cell.

[215]  P. Friedl,et al.  Collective cell migration: guidance principles and hierarchies. , 2015, Trends in cell biology.

[216]  Stephen Brown,et al.  Unphosphorylated STATs go nuclear. , 2008, Current opinion in genetics & development.

[217]  K. Rakesh,et al.  Controlling cytokine signaling by constitutive inhibitors. , 2005, Biochemical pharmacology.

[218]  R. Schuh,et al.  A transcription unit at the ken and barbie gene locus encodes a novel Drosophila zinc finger protein , 1998, Mechanisms of Development.

[219]  S. Akira,et al.  Selective activation of STAT5 unveils its role in stem cell self-renewal in normal and leukemic hematopoiesis , 2005, The Journal of experimental medicine.

[220]  John J. O’Shea,et al.  Modulation of Innate and Adaptive Immune Responses by Tofacitinib (CP-690,550) , 2011, The Journal of Immunology.

[221]  J. Kovarik,et al.  JAK/STAT signaling pathways and cancer. Janus kinases/signal transducers and activators of transcription. , 2002, Neoplasma.

[222]  J. Leatherman,et al.  Germline self-renewal requires cyst stem cells, while stat regulates niche adhesion in Drosophila testes , 2010, Nature Cell Biology.

[223]  J. Yun,et al.  miR-625 suppresses tumour migration and invasion by targeting IGF2BP1 in hepatocellular carcinoma , 2014, Oncogene.

[224]  R. Sun,et al.  miR-506 inhibits the proliferation and invasion by targeting IGF2BP1 in glioblastoma. , 2015, American journal of translational research.

[225]  Stephen Brown,et al.  The Fertile Field of Drosophila JAK/STAT Signalling , 2002, Current Biology.

[226]  Chi Zhang,et al.  UBAP2 negatively regulates the invasion of hepatocellular carcinoma cell by ubiquitinating and degradating Annexin A2 , 2016, Oncotarget.

[227]  D. Montell,et al.  Requirement for JAK/STAT signaling throughout border cell migration in Drosophila , 2005, Development.

[228]  J. Gutkind,et al.  mom identifies a receptor for the Drosophila JAK/STAT signal transduction pathway and encodes a protein distantly related to the mammalian cytokine receptor family. , 2002, Genes & development.

[229]  Amanda J. Monahan,et al.  Socs36E limits STAT signaling via Cullin2 and a SOCS-box independent mechanism in the Drosophila egg chamber , 2015, Mechanisms of Development.

[230]  Ermir Qeli,et al.  A Mighty Small Heart: The Cardiac Proteome of Adult Drosophila melanogaster , 2011, PloS one.

[231]  M. Ferrer,et al.  Allosteric Inhibitors of the Eya2 Phosphatase Are Selective and Inhibit Eya2-mediated Cell Migration* , 2014, The Journal of Biological Chemistry.

[232]  B. Leiby,et al.  Pharmacologic Inhibition of Jak2–Stat5 Signaling By Jak2 Inhibitor AZD1480 Potently Suppresses Growth of Both Primary and Castrate-Resistant Prostate Cancer , 2013, Clinical Cancer Research.

[233]  Xiaorong Wu,et al.  Upregulation of the Drosophila Friend of GATA Gene u-shaped by JAK/STAT Signaling Maintains Lymph Gland Prohemocyte Potency , 2009, Molecular and Cellular Biology.

[234]  B. Leiby,et al.  TUMORIGENESIS AND NEOPLASTIC PROGRESSION Jak 2-Stat 5 a / b Signaling Induces Epithelial-to-Mesenchymal Transition and Stem-Like Cell Properties in Prostate Cancer , 2022 .

[235]  P. Escobar,et al.  Ovarian cancer immuno-reactive antigen domain containing 1 (OCIAD1), a key player in ovarian cancer cell adhesion. , 2008, Gynecologic oncology.

[236]  J. Darnell,et al.  The JAK-STAT pathway at twenty. , 2012, Immunity.

[237]  N. Aoki,et al.  A Cytosolic Protein-tyrosine Phosphatase PTP1B Specifically Dephosphorylates and Deactivates Prolactin-activated STAT5a and STAT5b* , 2000, The Journal of Biological Chemistry.

[238]  E. Hafen,et al.  Csk differentially regulates Src64 during distinct morphological events in Drosophila germ cells , 2006, Development.

[239]  B. Leiby,et al.  Inhibition of Stat5a/b Enhances Proteasomal Degradation of Androgen Receptor Liganded by Antiandrogens in Prostate Cancer , 2014, Molecular Cancer Therapeutics.

[240]  Q. Fan,et al.  STAT3 activation by IL-6 from mesenchymal stem cells promotes the proliferation and metastasis of osteosarcoma. , 2012, Cancer letters.

[241]  J. Lengyel,et al.  It takes guts: the Drosophila hindgut as a model system for organogenesis. , 2002, Developmental biology.

[242]  Hiu Kiu,et al.  SOCS regulation of the JAK/STAT signalling pathway. , 2008, Seminars in cell & developmental biology.

[243]  H. Klocker,et al.  PIAS1 is a determinant of poor survival and acts as a positive feedback regulator of AR signaling through enhanced AR stabilization in prostate cancer , 2015, Oncogene.

[244]  J. Yates,et al.  Rasputin Functions as a Positive Regulator of Orb in Drosophila Oogenesis , 2013, PloS one.

[245]  A. Lampin-Saint-Amaux,et al.  Cytokine signaling through the JAK/STAT pathway is required for long-term memory in Drosophila , 2011, Proceedings of the National Academy of Sciences.

[246]  Z. Ram,et al.  The Expression of Three Genes in Primary Non–Small Cell Lung Cancer Is Associated with Metastatic Spread to the Brain , 2009, Clinical Cancer Research.

[247]  L. Lessard,et al.  PTP1B is an androgen receptor-regulated phosphatase that promotes the progression of prostate cancer. , 2012, Cancer research.

[248]  B. Dréno,et al.  Loss of oncostatin M receptor beta in metastatic melanoma cells. , 2007, Oncogene.

[249]  M. Inamdar,et al.  A double helical motif in OCIAD2 is essential for its localization, interactions and STAT3 activation , 2018, Scientific Reports.

[250]  O. Silvennoinen,et al.  The Janus kinases (Jaks) , 2004, Genome Biology.

[251]  A. Dar,et al.  Prognostic Impact of PHIP Copy Number in Melanoma: Linkage to Ulceration , 2013, The Journal of investigative dermatology.

[252]  Willis X. Li,et al.  JAK signaling globally counteracts heterochromatic gene silencing , 2006, Nature Genetics.

[253]  B. Loppin,et al.  Intellectual disability‐associated dBRWD3 regulates gene expression through inhibition of HIRA/YEM‐mediated chromatin deposition of histone H3.3 , 2015, EMBO reports.

[254]  S. Majid,et al.  BPTF transduces MITF-driven prosurvival signals in melanoma cells , 2016, Proceedings of the National Academy of Sciences.

[255]  M. Inamdar.  Drosophila asrij is expressed in pole cells, trachea and hemocytes , 2003, Development Genes and Evolution.

[256]  Seymour Benzer,et al.  The eyes absent gene: Genetic control of cell survival and differentiation in the developing Drosophila eye , 1993, Cell.

[257]  J. Pierre,et al.  JAK/STAT signal transduction: regulators and implication in hematological malignancies. , 2006, Biochemical pharmacology.

[258]  E. Matunis,et al.  The Drosophila BCL6 homolog Ken and Barbie promotes somatic stem cell self-renewal in the testis niche. , 2012, Developmental biology.

[259]  R. Yelensky,et al.  Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence , 2016, Science Translational Medicine.

[260]  Zhiyu Zheng,et al.  Competitiveness for the niche and mutual dependence of the germline and somatic stem cells in the Drosophila testis are regulated by the JAK/STAT signaling , 2010, Journal of cellular physiology.

[261]  Shehua Qian,et al.  Chronic inflammation: key player and biomarker-set to predict and prevent cancer development and progression based on individualized patient profiles , 2019, EPMA Journal.

[262]  D. Hilton,et al.  Inhibitors of Cytokine Signal Transduction* , 2004, Journal of Biological Chemistry.

[263]  N. Perrimon,et al.  Polarity determination in the Drosophila eye: a novel role for unpaired and JAK/STAT signaling. , 1999, Genes & development.

[264]  D. Hilton,et al.  Negative regulation of the JAK/STAT pathway , 1999, BioEssays : news and reviews in molecular, cellular and developmental biology.

[265]  O. Stoeltzing,et al.  STAT5b as molecular target in pancreatic cancer--inhibition of tumor growth, angiogenesis, and metastases. , 2012, Neoplasia.

[266]  D. Larson,et al.  Csk-deficient boundary cells are eliminated from normal Drosophila epithelia by exclusion, migration, and apoptosis. , 2006, Developmental cell.

[267]  B. Loppin,et al.  Intellectual disability‐associated dBRWD3 regulates gene expression through inhibition of HIRA/YEM‐mediated chromatin deposition of histone H3.3 , 2015, EMBO reports.

[268]  A. Hoeflich,et al.  Interleukin-6 stimulates clonogenic growth of primary and metastatic human colon carcinoma cells. , 2000, Cancer letters.

[269]  L. Dai,et al.  The effect of quercetin nanoparticle on cervical cancer progression by inducing apoptosis, autophagy and anti-proliferation via JAK2 suppression. , 2016, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[270]  A. Kiger,et al.  Stem Cell Self-Renewal Specified by JAK-STAT Activation in Response to a Support Cell Cue , 2001, Science.

[271]  M. Inamdar,et al.  ARF1–GTP regulates Asrij to provide endocytic control of Drosophila blood cell homeostasis , 2014, Proceedings of the National Academy of Sciences.

[272]  B. Kennedy,et al.  Protein tyrosine phosphatase 1B deficiency or inhibition delays ErbB2-induced mammary tumorigenesis and protects from lung metastasis , 2007, Nature Genetics.

[273]  S. Constantinescu,et al.  Implications of STAT3 and STAT5 signaling on gene regulation and chromatin remodeling in hematopoietic cancer , 2018, Leukemia.

[274]  Stephen Brown,et al.  JAK/STAT signalling in Drosophila controls cell motility during germ cell migration , 2006, Developmental dynamics : an official publication of the American Association of Anatomists.

[275]  D. Harrison,et al.  JAK signaling is somatically required for follicle cell differentiation in Drosophila. , 2002, Development.

[276]  R. Read,et al.  Drosophila C-Terminal Src Kinase Negatively Regulates Organ Growth and Cell Proliferation through Inhibition of the Src, Jun N-Terminal Kinase, and STAT Pathways , 2004, Molecular and Cellular Biology.

[277]  M. Starz-Gaiano,et al.  Cytokine exocytosis and JAK/STAT activation in the Drosophila ovary requires the vesicle trafficking regulator α-Snap , 2018, Journal of Cell Science.

[278]  Jun Xie,et al.  Down-regulation of RE-1 silencing transcription factor (REST) in advanced prostate cancer by hypoxia-induced miR-106b~25. , 2014, Experimental cell research.

[279]  M. Krahn,et al.  Src kinases mediate the interaction of the apical determinant Bazooka/PAR3 with STAT92E and increase signalling efficiency in Drosophila ectodermal cells , 2013, Development.

[280]  J. Blaquiere,et al.  Hipk is required for JAK/STAT activity during development and tumorigenesis , 2019, PloS one.

[281]  Hong Zhang,et al.  Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in cancer , 2018, Journal of Hematology & Oncology.

[282]  Christina H. Stuelten,et al.  Cell motility in cancer invasion and metastasis: insights from simple model organisms , 2018, Nature Reviews Cancer.

[283]  T. Jinks,et al.  The JAK/STAT signaling pathway is required for the initial choice of sexual identity in Drosophila melanogaster. , 2000, Molecular cell.

[284]  D. Yamamoto,et al.  The ken and barbie gene encoding a putative transcription factor with a BTB domain and three zinc finger motifs functions in terminalia development of Drosophila. , 2003, Archives of insect biochemistry and physiology.

[285]  R. Birner-Gruenberger,et al.  Gel‐free mass spectrometry analysis of Drosophila melanogaster heads , 2015, Proteomics.

[286]  Ting-feng Wu,et al.  CEBPD amplification and overexpression in urothelial carcinoma: a driver of tumor metastasis indicating adverse prognosis , 2015, Oncotarget.

[287]  Norbert Perrimon,et al.  The roles of JAK/STAT signaling in Drosophila immune responses , 2004, Immunological reviews.

[288]  R Berger,et al.  A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. , 1997, Science.

[289]  N. Perrimon,et al.  Activation of a Drosophila Janus kinase (JAK) causes hematopoietic neoplasia and developmental defects. , 1995, The EMBO journal.

[290]  T. Schlenke,et al.  Insights from natural host-parasite interactions: the Drosophila model. , 2014, Developmental and comparative immunology.

[291]  G. Ferbeyre,et al.  SOCS1 inhibits migration and invasion of prostate cancer cells, attenuates tumor growth and modulates the tumor stroma , 2016, Prostate Cancer and Prostatic Diseases.

[292]  J. Lengyel,et al.  Localized JAK/STAT signaling is required for oriented cell rearrangement in a tubular epithelium , 2003, Development.

[293]  D. Harrison,et al.  Tools and methods for studying the Drosophila JAK/STAT pathway. , 2014, Methods.

[294]  D. Montell,et al.  Paracrine Signaling through the JAK/STAT Pathway Activates Invasive Behavior of Ovarian Epithelial Cells in Drosophila , 2001, Cell.

[295]  R. Lanot,et al.  Postembryonic hematopoiesis in Drosophila. , 2001, Developmental biology.

[296]  L. Gilboa,et al.  Without children is required for Stat-mediated zfh1 transcription and for germline stem cell differentiation , 2014, Development.

[297]  E. Hafen,et al.  The RNA-binding Proteins FMR1, Rasputin and Caprin Act Together with the UBA Protein Lingerer to Restrict Tissue Growth in Drosophila melanogaster , 2013, PLoS genetics.

[298]  Sylvain Pradervand,et al.  Drosophila intestinal response to bacterial infection: activation of host defense and stem cell proliferation. , 2009, Cell host & microbe.

[299]  M. Amoyel,et al.  JAK/STAT pathway dysregulation in tumors: a Drosophila perspective. , 2014, Seminars in cell & developmental biology.

[300]  Wen-yu Su,et al.  Inhibition of STAT5 induces G1 cell cycle arrest and reduces tumor cell invasion in human colorectal cancer cells , 2009, Laboratory Investigation.

[301]  Ping Chen,et al.  Protein inhibitor of activated STAT-1 is downregulated in gastric cancer tissue and involved in cell metastasis. , 2012, Oncology reports.

[302]  D. Barford,et al.  TYK2 and JAK2 Are Substrates of Protein-tyrosine Phosphatase 1B* , 2001, The Journal of Biological Chemistry.