Contextual determinants of TGFβ action in development, immunity and cancer

[1]  M. Whitman,et al.  A transcriptional partner for MAD proteins in TGF-beta signalling. , 1996, Nature.

[2]  K. Miyazono,et al.  Regulation of TGF-β Family Signaling by Inhibitory Smads. , 2017, Cold Spring Harbor perspectives in biology.

[3]  Jeffrey L. Wrana,et al.  Mechanism of activation of the TGF-β receptor , 1994, Nature.

[4]  Paul Tempst,et al.  Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-beta signaling. , 2009, Molecular cell.

[5]  K. Miyazono,et al.  Characterization of a bone morphogenetic protein-responsive Smad-binding element. , 2000, Molecular biology of the cell.

[6]  J. Wolchok,et al.  Blockade of surface-bound TGF-β on regulatory T cells abrogates suppression of effector T cell function in the tumor microenvironment , 2017, Science Signaling.

[7]  A. Balmain,et al.  Metastasis is driven by sequential elevation of H-ras and Smad2 levels , 2002, Nature Cell Biology.

[8]  J. Massagué,et al.  TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. , 2005, Cancer cell.

[9]  A. Donovan,et al.  Blocking extracellular activation of myostatin as a strategy for treating muscle wasting , 2018, Scientific Reports.

[10]  P. Hoodless,et al.  Smad2 and Smad3 positively and negatively regulate TGF beta-dependent transcription through the forkhead DNA-binding protein FAST2. , 1998, Molecular cell.

[11]  J. Massagué,et al.  Structural determinants of Smad function in TGF-β signaling. , 2015, Trends in biochemical sciences.

[12]  J. Massagué TGFβ signalling in context , 2012, Nature Reviews Molecular Cell Biology.

[13]  X. Qi,et al.  Induction of primordial germ cells from murine epiblasts by synergistic action of BMP4 and BMP8B signaling pathways , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Scott E. Kern,et al.  DPC4, A Candidate Tumor Suppressor Gene at Human Chromosome 18q21.1 , 1996, Science.

[15]  G. Sapkota,et al.  Phosphatases in SMAD regulation , 2012, FEBS letters.

[16]  C. Glass,et al.  Towards an understanding of cell-specific functions of signal-dependent transcription factors. , 2013, Journal of molecular endocrinology.

[17]  Ming O. Li,et al.  Transforming growth factor-beta signaling curbs thymic negative selection promoting regulatory T cell development. , 2010, Immunity.

[18]  J. Massagué,et al.  Metastatic colonization by circulating tumour cells , 2016, Nature.

[19]  J. Picard,et al.  AMH and AMH receptor defects in persistent Müllerian duct syndrome. , 2005, Human reproduction update.

[20]  M. Quintanilla,et al.  Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions. , 2003, The Journal of biological chemistry.

[21]  K. Luo Ski and SnoN: negative regulators of TGF-beta signaling. , 2004, Current opinion in genetics & development.

[22]  E. Fuchs,et al.  Loss of TGFbeta signaling destabilizes homeostasis and promotes squamous cell carcinomas in stratified epithelia. , 2007, Cancer cell.

[23]  C. Hill,et al.  TGF-β signaling to chromatin: how Smads regulate transcription during self-renewal and differentiation. , 2014, Seminars in cell & developmental biology.

[24]  T. Ichisaka,et al.  Nanog co-regulated by Nodal/Smad2 and Oct4 is required for pluripotency in developing mouse epiblast. , 2014, Developmental biology.

[25]  Xiao-Fan Wang,et al.  Signaling cross-talk between TGF-β/BMP and other pathways , 2009, Cell Research.

[26]  J. Massagué,et al.  The p53 Family Coordinates Wnt and Nodal Inputs in Mesendodermal Differentiation of Embryonic Stem Cells. , 2017, Cell stem cell.

[27]  Tessa G. Montague,et al.  Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm , 2017, eLife.

[28]  C. Iacobuzio-Donahue,et al.  TGF-β Tumor Suppression through a Lethal EMT , 2016, Cell.

[29]  J. Massagué,et al.  TGFβ in Cancer , 2008, Cell.

[30]  J. Wallingford,et al.  P53 activity is essential for normal development in Xenopus , 1997, Current Biology.

[31]  Maria I Morasso,et al.  Dlx3 is a crucial regulator of hair follicle differentiation and cycling , 2008, Development.

[32]  M. Trotter,et al.  Pluripotency factors regulate definitive endoderm specification through eomesodermin. , 2011, Genes & development.

[33]  Jeffrey L. Wrana,et al.  TGFβ signals through a heteromeric protein kinase receptor complex , 1992, Cell.

[34]  J. Massagué,et al.  Mechanisms of TGF-β Signaling from Cell Membrane to the Nucleus , 2003, Cell.

[35]  R. Fleming,et al.  Bone morphogenetic proteins as regulators of iron metabolism. , 2014, Annual review of nutrition.

[36]  T. B. Thompson,et al.  The DAN family: Modulators of TGF‐β signaling and beyond , 2014, Protein science : a publication of the Protein Society.

[37]  M. Ascano,et al.  Augmented noncanonical BMP type II receptor signaling mediates the synaptic abnormality of fragile X syndrome , 2016, Science Signaling.

[38]  Camille Stephan-Otto Attolini,et al.  TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis , 2018, Nature.

[39]  J. Stavnezer,et al.  Analysis of transforming growth factor‐β1‐induced Ig germ‐line γ2b transcription and its implication for IgA isotype switching , 2005, European journal of immunology.

[40]  H. Moses,et al.  Growth inhibitor from BSC-1 cells closely related to platelet type beta transforming growth factor. , 1984, Science.

[41]  D. Kessler,et al.  Transcriptional integration of Wnt and Nodal pathways in establishment of the Spemann organizer. , 2012, Developmental biology.

[42]  R. Burdine,et al.  Gdf3 is required for robust Nodal signaling during germ layer formation and left-right patterning , 2017, eLife.

[43]  K. Burns,et al.  Genetics of mammalian reproduction: modeling the end of the germline. , 2012, Annual review of physiology.

[44]  M. Sporn,et al.  Polypeptide transforming growth factors isolated from bovine sources and used for wound healing in vivo. , 1983, Science.

[45]  J. Wrana,et al.  Switch enhancers interpret TGF-β and Hippo signaling to control cell fate in human embryonic stem cells. , 2013, Cell reports.

[46]  H. Friess,et al.  Enhanced expression of transforming growth factor β isoforms in pancreatic cancer correlates with decreased survival , 1993 .

[47]  J. Massagué,et al.  Transforming growth factor (cid:1) -induced cell cycle arrest of human hematopoietic cells requires p57KIP2 up-regulation , 2022 .

[48]  Shawn C. Little,et al.  BMP heterodimers assemble hetero-type I receptor complexes that pattern the DV axis , 2009, Nature Cell Biology.

[49]  Shinichiro,et al.  Carcinoma , 1906, The Hospital.

[50]  J. Massagué,et al.  Structural basis for genome wide recognition of 5-bp GC motifs by SMAD transcription factors , 2017, Nature Communications.

[51]  H. Yost,et al.  Maternal Gdf3 is an obligatory cofactor in Nodal signaling for embryonic axis formation in zebrafish , 2017, eLife.

[52]  H. Othmer,et al.  Facilitated Transport of a Dpp/Scw Heterodimer by Sog/Tsg Leads to Robust Patterning of the Drosophila Blastoderm Embryo , 2005, Cell.

[53]  J. Massagué,et al.  Mechanisms of TGF-beta signaling from cell membrane to the nucleus. , 2003, Cell.

[54]  A. Madi,et al.  The transcription factor musculin promotes the unidirectional development of peripheral Treg cells by suppressing the TH2 transcriptional program , 2017, Nature Immunology.

[55]  K. Luo Ski and SnoN: negative regulators of TGF-β signaling , 2004 .

[56]  Yue Zhang,et al.  Regulation of the Polarity Protein Par6 by TGFß Receptors Controls Epithelial Cell Plasticity , 2005, Science.

[57]  H. Friess,et al.  Enhanced expression of the type II transforming growth factor-beta receptor is associated with decreased survival in human pancreatic cancer. , 1999, Pancreas.

[58]  S. Anderson,et al.  Integration of Smad and Forkhead Pathways in the Control of Neuroepithelial and Glioblastoma Cell Proliferation , 2004, Cell.

[59]  S. Newfeld,et al.  Regulation of TGF‐β signal transduction by mono‐ and deubiquitylation of Smads , 2012, FEBS letters.

[60]  R. Derynck,et al.  The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for smad3 in TGF-beta-induced transcriptional activation. , 1998, Genes & development.

[61]  E. Fuchs,et al.  The harmonies played by TGF-β in stem cell biology. , 2012, Cell stem cell.

[62]  James M. Roberts,et al.  Cloning of p27 Kip1 , a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals , 1994, Cell.

[63]  Ken W. Y. Cho,et al.  Foxh1 Occupies cis-Regulatory Modules Prior to Dynamic Transcription Factor Interactions Controlling the Mesendoderm Gene Program. , 2017, Developmental cell.

[64]  W. Vale,et al.  Roles of activin family in pancreatic development and homeostasis , 2012, Molecular and Cellular Endocrinology.

[65]  Roger A. Pedersen,et al.  Brachyury and SMAD signalling collaboratively orchestrate distinct mesoderm and endoderm gene regulatory networks in differentiating human embryonic stem cells , 2015, Development.

[66]  Gerald C. Chu,et al.  SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression , 2011, Nature.

[67]  Aaron M Zorn,et al.  Vertebrate endoderm development and organ formation. , 2009, Annual review of cell and developmental biology.

[68]  Gerhard Christofori,et al.  Epithelial-mesenchymal transition (EMT) and metastasis: yes, no, maybe? , 2016, Current opinion in cell biology.

[69]  D. de Sanctis,et al.  Supplemental Information Structural Basis of the Human Endoglin-BMP 9 Interaction : Insights into BMP Signaling and HHT 1 , 2017 .

[70]  Yibin Kang,et al.  Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells. , 2011, Cancer cell.

[71]  J. Massagué,et al.  Physical and Functional Interaction of SMADs and p300/CBP* , 1998, The Journal of Biological Chemistry.

[72]  Y. Kalaidzidis,et al.  Kinetics of Morphogen Gradient Formation , 2007, Science.

[73]  Minoru Watanabe,et al.  Smad4 and FAST-1 in the assembly of activin-responsive factor , 1997, Nature.

[74]  C. Heldin TGF-beta signaling from receptors to Smads , 2008 .

[75]  T. Hunter,et al.  TGF-beta-stimulated cooperation of smad proteins with the coactivators CBP/p300. , 1998, Genes & development.

[76]  A. Brivanlou,et al.  Dephosphorylation of the Linker Regions of Smad1 and Smad2/3 by Small C-terminal Domain Phosphatases Has Distinct Outcomes for Bone Morphogenetic Protein and Transforming Growth Factor-β Pathways* , 2006, Journal of Biological Chemistry.

[77]  E. Robertis,et al.  Integrating Patterning Signals: Wnt/GSK3 Regulates the Duration of the BMP/Smad1 Signal , 2007, Cell.

[78]  Shyam Prabhakar,et al.  Structure of Smad1 MH1/DNA complex reveals distinctive rearrangements of BMP and TGF-β effectors , 2010, Nucleic acids research.

[79]  Xin-Hua Feng,et al.  Smad2 Positively Regulates the Generation of Th17 Cells* , 2010, The Journal of Biological Chemistry.

[80]  A. Rudensky,et al.  Regulatory T cells: mechanisms of differentiation and function. , 2012, Annual review of immunology.

[81]  T. Springer,et al.  Force interacts with macromolecular structure in activation of TGF-β , 2017, Nature.

[82]  Richard A. Flavell,et al.  Mechanism of Transforming Growth Factor β–induced Inhibition of T Helper Type 1 Differentiation , 2002, The Journal of experimental medicine.

[83]  C. Hill,et al.  Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF-beta receptor activity. , 2002, Molecular cell.

[84]  J. Chirgwin,et al.  Transforming growth factor-beta stimulates parathyroid hormone-related protein and osteolytic metastases via Smad and mitogen-activated protein kinase signaling pathways. , 2002, The Journal of biological chemistry.

[85]  Michael B. Elowitz,et al.  Combinatorial Signal Perception in the BMP Pathway , 2017, Cell.

[86]  C. Heldin,et al.  Mechanisms of TGFβ-Induced Epithelial–Mesenchymal Transition , 2016, Journal of clinical medicine.

[87]  Elaine Fuchs,et al.  TGF-β Promotes Heterogeneity and Drug Resistance in Squamous Cell Carcinoma , 2015, Cell.

[88]  Raymond B. Runyan,et al.  Slug is an essential target of TGFbeta2 signaling in the developing chicken heart. , 2000, Developmental biology.

[89]  David M Reynolds,et al.  Signaling network crosstalk in human pluripotent cells: a Smad2/3-regulated switch that controls the balance between self-renewal and differentiation. , 2012, Cell stem cell.

[90]  Takeshi Imamura,et al.  Role of Ras Signaling in the Induction of Snail by Transforming Growth Factor-β* , 2009, Journal of Biological Chemistry.

[91]  A. Brivanlou,et al.  Balancing BMP signaling through integrated inputs into the Smad1 linker. , 2007, Molecular cell.

[92]  Yigong Shi,et al.  Crystal Structure of a Smad MH1 Domain Bound to DNA Insights on DNA Binding in TGF-β Signaling , 1998, Cell.

[93]  Bond-Smith Giles,et al.  Only women with symptoms need to have their breast implants removed, says government , 2012 .

[94]  T. Kornberg,et al.  Dependence of Drosophila wing imaginal disc cytonemes on Decapentaplegic , 2005, Nature.

[95]  B. Song,et al.  Smad2 and Smad3 Regulate Chondrocyte Proliferation and Differentiation in the Growth Plate , 2016, PLoS genetics.

[96]  Shuichi Tsutsumi,et al.  ChIP-seq reveals cell type-specific binding patterns of BMP-specific Smads and a novel binding motif , 2011, Nucleic acids research.

[97]  George Q. Daley,et al.  Lineage Regulators Direct BMP and Wnt Pathways to Cell-Specific Programs during Differentiation and Regeneration , 2011, Cell.

[98]  Florence March,et al.  2016 , 2016, Affair of the Heart.

[99]  J. Wrana,et al.  TGF-β Family Signaling in Embryonic and Somatic Stem-Cell Renewal and Differentiation. , 2017, Cold Spring Harbor perspectives in biology.

[100]  Fang Liu,et al.  Cyclin-dependent kinases regulate the antiproliferative function of Smads , 2004, Nature.

[101]  H. Moses,et al.  The roles of TGFβ in the tumour microenvironment , 2013, Nature Reviews Cancer.

[102]  Janet Rossant,et al.  The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-β-SMAD pathway. , 2010, Developmental cell.

[103]  R. Derynck,et al.  TGF-beta induced transdifferentiation of mammary epithelial cells to mesenchymal cells: involvement of type I receptors , 1994, The Journal of cell biology.

[104]  J. Wrana,et al.  Activation of LIMK1 by binding to the BMP receptor, BMPRII, regulates BMP‐dependent dendritogenesis , 2004, The EMBO journal.

[105]  S. Dupont,et al.  Links between Tumor Suppressors p53 Is Required for TGF-β Gene Responses by Cooperating with Smads , 2003, Cell.

[106]  T. Nomura,et al.  Control of Regulatory T Cell Development by the Transcription Factor Foxp3 , 2002 .

[107]  G. Hannon,et al.  p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. , 1994, Nature.

[108]  T. Tan,et al.  Epithelial-mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients , 2014, EMBO molecular medicine.

[109]  H. Dietz,et al.  The genetic basis of aortic aneurysm. , 2014, Cold Spring Harbor perspectives in medicine.

[110]  R. Young,et al.  Super-Enhancers in the Control of Cell Identity and Disease , 2013, Cell.

[111]  Yuelei Shen,et al.  TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function , 2008, Nature.

[112]  B. Ozdamar Receptors Controls Epithelial Cell Plasticity Regulation of the Polarity Protein Par6 by TGFß , 2007 .

[113]  J. Berzofsky,et al.  Blockade of only TGF-β 1 and 2 is sufficient to enhance the efficacy of vaccine and PD-1 checkpoint blockade immunotherapy , 2017, Oncoimmunology.

[114]  Charles Y. Lin,et al.  Convergence of developmental and oncogenic signaling pathways at transcriptional super-enhancers. , 2015, Molecular cell.

[115]  J. Wrana,et al.  Foxh1 recruits Gsc to negatively regulate Mixl1 expression during early mouse development , 2007, The EMBO journal.

[116]  Andrew C. Nelson,et al.  In Vivo Regulation of the Zebrafish Endoderm Progenitor Niche by T-Box Transcription Factors , 2017, Cell reports.

[117]  David A. Orlando,et al.  Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes , 2013, Cell.

[118]  R. Sandberg,et al.  BMP signaling and its pSMAD1/5 target genes differentially regulate hair follicle stem cell lineages. , 2014, Cell stem cell.

[119]  K. Furuuchi,et al.  Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer , 2008, Nature Immunology.

[120]  T. Watabe,et al.  Molecular mechanisms of Spemann's organizer formation: conserved growth factor synergy between Xenopus and mouse. , 1995, Genes & development.

[121]  N. Ling,et al.  Pituitary FSH Is Released by a Heterodimer of the β-Subunits from the Two Forms of Inhibin , 1987 .

[122]  D. Patel,et al.  A Poised Chromatin Platform for TGF-β Access to Master Regulators , 2011, Cell.

[123]  Yigong Shi,et al.  A structural basis for mutational inactivation of the tumour suppressor Smad4 , 1997, Nature.

[124]  Gerald C. Chu,et al.  Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. , 2006, Genes & development.

[125]  K. Kinzler,et al.  Human Smad3 and Smad4 are sequence-specific transcription activators. , 1998, Molecular cell.

[126]  P. Jung,et al.  Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation. , 2012, Cancer cell.

[127]  A. Hinck,et al.  Structural Biology and Evolution of the TGF-β Family. , 2016, Cold Spring Harbor perspectives in biology.

[128]  Samy Lamouille,et al.  Emergence of the Phosphoinositide 3-Kinase-Akt- Mammalian Target of Rapamycin Axis in Transforming Growth Factor-β-Induced Epithelial-Mesenchymal Transition , 2010, Cells Tissues Organs.

[129]  Benjamin E. Gross,et al.  Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal , 2013, Science Signaling.

[130]  R. Derynck,et al.  Structural and Functional Characterization of the Transforming Growth Factor-β-induced Smad3/c-Jun Transcriptional Cooperativity* , 2000, The Journal of Biological Chemistry.

[131]  P. ten Dijke,et al.  BMP signaling in vascular diseases , 2012, FEBS letters.

[132]  M. Sporn,et al.  Type beta transforming growth factor: a bifunctional regulator of cellular growth. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[133]  J. Massagué,et al.  A Smad action turnover switch operated by WW domain readers of a phosphoserine code. , 2011, Genes & development.

[134]  A. Hata,et al.  TGF-β Signaling from Receptors to Smads. , 2016, Cold Spring Harbor perspectives in biology.

[135]  Camille Stephan-Otto Attolini,et al.  Stromal gene expression defines poor-prognosis subtypes in colorectal cancer , 2015, Nature Genetics.

[136]  T. Yamashita,et al.  RGMs: Structural Insights, Molecular Regulation, and Downstream Signaling. , 2017, Trends in cell biology.

[137]  E. Jimi,et al.  Smad9 is a new type of transcriptional regulator in bone morphogenetic protein signaling , 2014, Scientific Reports.

[138]  Sha Tian,et al.  KLF5 Activates MicroRNA 200 Transcription To Maintain Epithelial Characteristics and Prevent Induced Epithelial-Mesenchymal Transition in Epithelial Cells , 2013, Molecular and Cellular Biology.

[139]  U. Hellman,et al.  PARP-1 attenuates Smad-mediated transcription. , 2010, Molecular cell.

[140]  E. D. De Robertis,et al.  Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural induction. , 2003, Genes & development.

[141]  J. Massagué How cells read TGF-beta signals. , 2000, Nature reviews. Molecular cell biology.

[142]  J. Massagué,et al.  A self-enabling TGFbeta response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells. , 2003, Molecular cell.

[143]  D. Littman,et al.  The Orphan Nuclear Receptor RORγt Directs the Differentiation Program of Proinflammatory IL-17+ T Helper Cells , 2006, Cell.

[144]  George Q. Daley,et al.  Lineage Regulators Direct BMP and Wnt Pathways to Cell-Specific Programs During Differentiation and Regeneration, , 2011 .

[145]  J. Massagué,et al.  Smad2 nucleocytoplasmic shuttling by nucleoporins CAN/Nup214 and Nup153 feeds TGFbeta signaling complexes in the cytoplasm and nucleus. , 2002, Molecular cell.

[146]  S. Germain,et al.  Homeodomain and winged-helix transcription factors recruit activated Smads to distinct promoter elements via a common Smad interaction motif. , 2000, Genes & development.

[147]  R. Schulte‐Hermann,et al.  Hepatocytes convert to a fibroblastoid phenotype through the cooperation of TGF-beta1 and Ha-Ras: steps towards invasiveness. , 2002, Journal of cell science.

[148]  Sho Fujisawa,et al.  Nuclear CDKs Drive Smad Transcriptional Activation and Turnover in BMP and TGF-β Pathways , 2009, Cell.

[149]  Hans Clevers,et al.  Signaling pathways in intestinal development and cancer. , 2004, Annual review of cell and developmental biology.

[150]  David A. Orlando,et al.  Master Transcription Factors Determine Cell-Type-Specific Responses to TGF-β Signaling , 2011, Cell.

[151]  Jeffrey L. Wrana,et al.  Signal integration in TGF-β, WNT, and Hippo pathways , 2013, F1000prime reports.

[152]  Elisa de Stanchina,et al.  Metastatic Latency and Immune Evasion through Autocrine Inhibition of WNT , 2016, Cell.

[153]  Xiao-ming Meng,et al.  TGF-β: the master regulator of fibrosis , 2016, Nature Reviews Nephrology.

[154]  V. Yang,et al.  Krüppel-like factor 5 is essential for proliferation and survival of mouse intestinal epithelial stem cells. , 2015, Stem cell research.

[155]  S. Jameson,et al.  Selection of self-reactive T cells in the thymus. , 2012, Annual review of immunology.

[156]  H. Ng,et al.  Regulatory crosstalk between lineage-survival oncogenes KLF5, GATA4 and GATA6 cooperatively promotes gastric cancer development , 2014, Gut.

[157]  C. Heldin,et al.  Signaling Receptors for TGF-β Family Members. , 2016, Cold Spring Harbor perspectives in biology.

[158]  G. Natoli,et al.  Dissection of transcriptional and cis‐regulatory control of differentiation in human pancreatic cancer , 2016, The EMBO journal.

[159]  J. Massagué,et al.  A Smad Transcriptional Corepressor , 1999, Cell.

[160]  Vicki Rosen,et al.  BMP signalling in skeletal development, disease and repair , 2016, Nature Reviews Endocrinology.

[161]  P. D. Kraan,et al.  The changing role of TGFβ in healthy, ageing and osteoarthritic joints , 2017, Nature Reviews Rheumatology.

[162]  Shawn M. Gillespie,et al.  Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer , 2017, Cell.

[163]  A. Iavarone,et al.  Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response to TGF-beta. , 1995, Genes & development.

[164]  Gregory J. Hannon,et al.  pl5INK4B is a potentia| effector of TGF-β-induced cell cycle arrest , 1994, Nature.

[165]  B. Keller,et al.  Interaction of TGFβ and BMP Signaling Pathways during Chondrogenesis , 2011, PloS one.

[166]  H. Frierson,et al.  Activation of Akt Signaling in Prostate Induces a TGFβ Mediated Restraint on Cancer Progression and Metastasis , 2013, Oncogene.

[167]  D. Littman,et al.  The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. , 2006, Cell.

[168]  Edward Chuong,et al.  Chromatin and transcriptional signatures for Nodal signaling during endoderm formation in hESCs. , 2011, Developmental biology.

[169]  L. Wakefield,et al.  Beyond TGFβ: roles of other TGFβ superfamily members in cancer , 2013, Nature Reviews Cancer.

[170]  H. Niwa,et al.  Maintenance of pluripotency in mouse ES cells without Trp53 , 2013, Scientific Reports.

[171]  M. Rugge,et al.  Germ-Layer Specification and Control of Cell Growth by Ectodermin, a Smad4 Ubiquitin Ligase , 2005, Cell.

[172]  E. Batlle,et al.  Targeting the Microenvironment in Advanced Colorectal Cancer. , 2016, Trends in cancer.

[173]  A. Stewart,et al.  Distinct modes of SMAD2 chromatin binding and remodeling shape the transcriptional response to NODAL/Activin signaling , 2017, eLife.

[174]  V. Lefebvre,et al.  The transcription factor Sox4 is a downstream target of signaling by the cytokine TGF-β and suppresses TH2 differentiation , 2012, Nature Immunology.

[175]  R. Bourgon,et al.  TGF-β attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells , 2018, Nature.

[176]  Wei He,et al.  Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[177]  A. Bassols,et al.  Two forms of transforming growth factor-β distinguished by multipotential haematopoietic progenitor cells , 1987, Nature.

[178]  A. Barski,et al.  Genomic integration of Wnt/β-catenin and BMP/Smad1 signaling coordinates foregut and hindgut transcriptional programs , 2017, Development.

[179]  David García-Dorado,et al.  TGF-beta increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma. , 2009, Cancer cell.

[180]  J. Chirgwin,et al.  Transforming Growth Factor-Stimulates Parathyroid Hormone-related Protein and Osteolytic Metastases via Smad and Mitogen-activated Protein Kinase Signaling Pathways * , 2002 .

[181]  J. Massagué,et al.  E2F4/5 and p107 as Smad Cofactors Linking the TGFβ Receptor to c-myc Repression , 2002, Cell.

[182]  Ming O. Li,et al.  Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection. , 2017, Cold Spring Harbor perspectives in biology.

[183]  J. Massagué,et al.  The transforming growth factor-β system, a complex pattern of cross-reactive ligands and receptors , 1987, Cell.

[184]  T. Sjöblom,et al.  Sustained TGF beta exposure suppresses Smad and non-Smad signalling in mammary epithelial cells, leading to EMT and inhibition of growth arrest and apoptosis. , 2008, Oncogene.

[185]  H. Moses,et al.  Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-beta signaling in cooperation with active Kras expression. , 2006, Genes & development.

[186]  N. Bardeesy,et al.  Pancreatic adenocarcinoma. , 2014, The New England journal of medicine.

[187]  Robert Walgate,et al.  Proliferation , 1985, Nature.

[188]  K. Kinzler,et al.  Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. , 1995, Science.

[189]  Osamu Shimmi,et al.  Facilitated Transport of a Dpp/Scw Heterodimer by Sog/Tsg Leads to Robust Patterning of the Drosophila Blastoderm Embryo , 2005, Cell.

[190]  J. Baker,et al.  HEB associates with PRC2 and SMAD2/3 to regulate developmental fates , 2015, Nature Communications.

[191]  M. Kretzschmar,et al.  Opposing BMP and EGF signalling pathways converge on the TGF-β family mediator Smad1 , 1997, Nature.

[192]  R. Haydon,et al.  Bone Morphogenetic Protein (BMP) signaling in development and human diseases , 2014, Genes & diseases.

[193]  J. Massagué,et al.  TGF beta signals through a heteromeric protein kinase receptor complex. , 1992, Cell.

[194]  R. Weinberg,et al.  Epithelial-Mesenchymal Plasticity: A Central Regulator of Cancer Progression. , 2015, Trends in cell biology.

[195]  R Wieser,et al.  Mechanism of activation of the TGF-beta receptor. , 1994, Nature.

[196]  G. Sapkota,et al.  The emerging roles of deubiquitylating enzymes (DUBs) in the TGFβ and BMP pathways , 2014, Cellular signalling.

[197]  T. Wirth,et al.  Transforming growth factor beta and cyclosporin A inhibit the inducible activity of the interleukin-2 gene in T cells through a noncanonical octamer-binding site , 1993, Molecular and cellular biology.

[198]  D. Brazil,et al.  BMP signalling: agony and antagony in the family. , 2015, Trends in cell biology.

[199]  Matthew Loose,et al.  A genetic regulatory network for Xenopus mesendoderm formation. , 2004, Developmental biology.

[200]  Robert A. Weinberg,et al.  Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. , 2008, Developmental cell.

[201]  R. Morita,et al.  Smad2 and Smad3 Are Redundantly Essential for the TGF-β–Mediated Regulation of Regulatory T Plasticity and Th1 Development , 2010, The Journal of Immunology.

[202]  Li Li,et al.  Conversion of Peripheral CD4+CD25− Naive T Cells to CD4+CD25+ Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3 , 2003, The Journal of experimental medicine.

[203]  K. Jones,et al.  SMADs and YAP compete to control elongation of β-catenin:LEF-1-recruited RNAPII during hESC differentiation. , 2015, Molecular cell.

[204]  P. Dijke,et al.  Immunoregulation by members of the TGFβ superfamily , 2016, Nature Reviews Immunology.

[205]  Piotr J. Balwierz,et al.  Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming. , 2013, Cancer cell.

[206]  D. L. Weeks,et al.  TGFbeta2 and TGFbeta3 have separate and sequential activities during epithelial-mesenchymal cell transformation in the embryonic heart. , 1999, Developmental biology.

[207]  Roger R. Gomis,et al.  TGFβ Primes Breast Tumors for Lung Metastasis Seeding through Angiopoietin-like 4 , 2008, Cell.

[208]  J. Wrana,et al.  BMP-2 and OP-1 exert direct and opposite effects on renal branching morphogenesis. , 1997, The American journal of physiology.

[209]  S. Pauklin,et al.  Activin/Nodal signalling in stem cells , 2015, Development.

[210]  H. Beug,et al.  TGF-beta1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. , 1996, Genes & development.

[211]  H. Aburatani,et al.  Genomewide Comprehensive Analysis Reveals Critical Cooperation Between Smad and c‐Fos in RANKL‐Induced Osteoclastogenesis , 2015, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[212]  A. Kotzsch,et al.  GDF-5 can act as a context-dependent BMP-2 antagonist , 2015, BMC Biology.

[213]  J. Massagué,et al.  OAZ Uses Distinct DNA- and Protein-Binding Zinc Fingers in Separate BMP-Smad and Olf Signaling Pathways , 2000, Cell.