Stathmin 1: a novel therapeutic target for anticancer activity

Stathmin 1 (STMN1), also known as p17, p18, p19, 19K, metablastin, oncoprotein 18, LAP 18 and Op18, is a 19 kDa cytosolic protein. It was the first discovered member of a family of phylogenetically related microtubule-destabilizing phosphoproteins critically involved in the construction and function of the mitotic spindle. A threshold level of STMN1 is required for orderly progression through mitosis in a variety of cell types. STMN1 is overexpressed across a broad range of human malignancies (leukemia, lymphoma, neuroblastoma; ovarian, prostatic, breast and lung cancers and mesothelioma). It is also upregulated in normally proliferating cell lines but is only rarely upregulated in nonproliferating cell lines with the exception of neurons, anterior pituitary cells and glial cells. Its expression is also upregulated in hepatocytes during regeneration and in lymphoid cells when they are signaled to proliferate. In this review, we summarize available data as rationale for the therapeutic manipulation of STMN1 in cancer patients.

[1]  M. Kirschner,et al.  Dynamic instability of microtubule growth , 1984, Nature.

[2]  David J. Anderson,et al.  The NGF-inducible SCG10 mRNA encodes a novel membrane-bound protein present in growth cones and abundant in developing neurons , 1988, Neuron.

[3]  R. Kuick,et al.  Identification of a polypeptide associated with the malignant phenotype in acute leukemia. , 1988, The Journal of biological chemistry.

[4]  J. Strahler,et al.  Characterization of the gene for a proliferation-related phosphoprotein (oncoprotein 18) expressed in high amounts in acute leukemia. , 1991, The Journal of biological chemistry.

[5]  L. Beretta,et al.  Multiple phosphorylation of stathmin. Identification of four sites phosphorylated in intact cells and in vitro by cyclic AMP-dependent protein kinase and p34cdc2. , 1993, The Journal of biological chemistry.

[6]  L. Beretta,et al.  Multiple phosphorylation of stathmin , 1993 .

[7]  G. Landberg,et al.  Quantitative analysis of the expression and regulation of an activation-regulated phosphoprotein (oncoprotein 18) in normal and neoplastic cells. , 1993, Leukemia.

[8]  G. Atweh,et al.  Expression of the leukemia-associated gene, p18, in normal and malignant tissues; inactivation of expression in a patient with cleaved B cell lymphoma/leukemia. , 1993, Oncogene.

[9]  U. Marklund,et al.  The phenotype of a "Cdc2 kinase target site-deficient" mutant of oncoprotein 18 reveals a role of this protein in cell cycle control. , 1994, Journal of Biological Chemistry.

[10]  G. Atweh,et al.  Regulation of phosphoprotein p18 in leukemic cells. Cell cycle regulated phosphorylation by p34cdc2 kinase. , 1994, The Journal of biological chemistry.

[11]  J. Garin,et al.  Induction of stathmin expression during erythropoietic differentiation. , 1995, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[12]  H. Gradin,et al.  Control of microtubule dynamics by oncoprotein 18: dissection of the regulatory role of multisite phosphorylation during mitosis , 1997, Molecular and cellular biology.

[13]  T. Mitchison,et al.  Microtubule polymerization dynamics. , 1997, Annual review of cell and developmental biology.

[14]  A. Sobel,et al.  SCLIP: A Novel SCG10‐Like Protein of the Stathmin Family Expressed in the Nervous System , 1998, Journal of neurochemistry.

[15]  O. Gavet,et al.  The stathmin phosphoprotein family: intracellular localization and effects on the microtubule network. , 1998, Journal of cell science.

[16]  S. El Mestikawy,et al.  Differential, regional, and cellular expression of the stathmin family transcripts in the adult rat brain , 1999, Journal of neuroscience research.

[17]  A. Levine,et al.  Transcriptional repression by wild-type p53 utilizes histone deacetylases, mediated by interaction with mSin3a. , 1999, Genes & development.

[18]  B. Howell,et al.  Dissociation of the tubulin-sequestering and microtubule catastrophe-promoting activities of oncoprotein 18/stathmin. , 1999, Molecular biology of the cell.

[19]  M. Pagano,et al.  Regulation of the Cdk inhibitor p27 and its deregulation in cancer , 2000, Journal of cellular physiology.

[20]  W. Fiers,et al.  Tumor Necrosis Factor-induced Microtubule Stabilization Mediated by Hyperphosphorylated Oncoprotein 18 Promotes Cell Death* , 2000, The Journal of Biological Chemistry.

[21]  G. Brattsand Correlation of oncoprotein 18/stathmin expression in human breast cancer with established prognostic factors , 2000, British Journal of Cancer.

[22]  P. Curmi,et al.  The 4 Å X-Ray Structure of a Tubulin:Stathmin-like Domain Complex , 2000, Cell.

[23]  S. Arkin,et al.  Taxol and anti-stathmin therapy: a synergistic combination that targets the mitotic spindle. , 2000, Cancer research.

[24]  Luis Serrano,et al.  Model for stathmin/OP18 binding to tubulin , 2000, The EMBO journal.

[25]  W. Jahnke,et al.  Op18/stathmin caps a kinked protofilament‐like tubulin tetramer , 2000, The EMBO journal.

[26]  J. Rossier,et al.  Probing the Native Structure of Stathmin and Its Interaction Domains with Tubulin , 2000, The Journal of Biological Chemistry.

[27]  S. Arkin,et al.  Effects of stathmin inhibition on the mitotic spindle. , 2001, Journal of cell science.

[28]  N. Cairns,et al.  Decreased protein levels of stathmin in adult brains with Down syndrome and Alzheimer's disease. , 2001, Journal of neural transmission. Supplementum.

[29]  L. Astic,et al.  Expression of SCG10 and stathmin proteins in the rat olfactory system during development and axonal regeneration , 2001, The Journal of comparative neurology.

[30]  A. Hall,et al.  Rac/Cdc42 and p65PAK Regulate the Microtubule-destabilizing Protein Stathmin through Phosphorylation at Serine 16* , 2001, The Journal of Biological Chemistry.

[31]  C. Benham,et al.  Development of ribozymes that target stathmin, a major regulator of the mitotic spindle. , 2001, Antisense & nucleic acid drug development.

[32]  P. Curmi,et al.  Stathmin Family Proteins Display Specific Molecular and Tubulin Binding Properties* , 2001, The Journal of Biological Chemistry.

[33]  N. Saijo,et al.  Oncoprotein 18 overexpression increases the sensitivity to vindesine in the human lung carcinoma cells , 2001, Cancer.

[34]  G. Atweh,et al.  Stathmin Inhibition Enhances Okadaic Acid-induced Mitotic Arrest , 2001, The Journal of Biological Chemistry.

[35]  R. Heald,et al.  Regulation of Op18 during Spindle Assembly in Xenopus Egg Extracts , 2001, The Journal of cell biology.

[36]  Ximing J. Yang,et al.  Gene expression profiling of favorable histology Wilms tumors and its correlation with clinical features. , 2002, Cancer research.

[37]  David E. Misek,et al.  Transforming properties of a Q18-->E mutation of the microtubule regulator Op18. , 2002, Cancer cell.

[38]  U. Schubart,et al.  Stathmin-deficient mice develop an age-dependent axonopathy of the central and peripheral nervous systems. , 2002, The American journal of pathology.

[39]  G. Atweh,et al.  Role of stathmin in the regulation of the mitotic spindle: potential applications in cancer therapy. , 2002, The Mount Sinai journal of medicine, New York.

[40]  J. Folkman Role of angiogenesis in tumor growth and metastasis. , 2002, Seminars in oncology.

[41]  I. Weinstein Addiction to Oncogenes--the Achilles Heal of Cancer , 2002, Science.

[42]  L. Cassimeris The oncoprotein 18/stathmin family of microtubule destabilizers. , 2002, Current opinion in cell biology.

[43]  W. Hait,et al.  Effect of stathmin on the sensitivity to antimicrotubule drugs in human breast cancer. , 2002, Cancer research.

[44]  G. Bepler,et al.  Transcripts in pretreatment biopsies from a three-arm randomized trial in metastatic non-small-cell lung cancer , 2003, Oncogene.

[45]  Robert A Gatenby,et al.  Application of quantitative models from population biology and evolutionary game theory to tumor therapeutic strategies. , 2003, Molecular cancer therapeutics.

[46]  W. Jahnke,et al.  Thermodynamics of the Op18/Stathmin-Tubulin Interaction* , 2003, Journal of Biological Chemistry.

[47]  David E. Misek,et al.  Overexpression of Oncoprotein 18 Correlates with Poor Differentiation in Lung Adenocarcinomas* , 2003, Molecular & Cellular Proteomics.

[48]  B. Day,et al.  Altered levels and regulation of stathmin in paclitaxel-resistant ovarian cancer cells , 2003, Oncogene.

[49]  M. Abe,et al.  Vascular Endothelial Zinc Finger 1 Is Involved in the Regulation of Angiogenesis: Possible Contribution of Stathmin/OP18 as a Downstream Target Gene , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[50]  P. Gao,et al.  [Significance of stathmin gene overexpression in osteosarcoma cells]. , 2004, Ai zheng = Aizheng = Chinese journal of cancer.

[51]  R. Serduc,et al.  Implication of bax in apoptosis depends on microtubule network mobility. , 2004, International journal of oncology.

[52]  G. Atweh,et al.  The role of stathmin in the regulation of the cell cycle , 2004, Journal of cellular biochemistry.

[53]  K. Nylander,et al.  Immunohistochemical detection of oncoprotein 18 (Op18) in malignant lymphomas , 1995, The Histochemical Journal.

[54]  G. Bokoch,et al.  Regulation of Microtubule Destabilizing Activity of Op18/Stathmin Downstream of Rac1* , 2004, Journal of Biological Chemistry.

[55]  Eric Karsenti,et al.  Stathmin-Tubulin Interaction Gradients in Motile and Mitotic Cells , 2004, Science.

[56]  J. Tseung Robbins and Cotran Pathologic Basis of Disease: 7th Edition , 2005 .

[57]  A. Vecchione,et al.  p27Kip1-stathmin interaction influences sarcoma cell migration and invasion , 2005 .

[58]  G. Atweh,et al.  Targeting stathmin in prostate cancer , 2005, Molecular Cancer Therapeutics.

[59]  Y. Jeng,et al.  Stathmin overexpression cooperates with p53 mutation and osteopontin overexpression, and is associated with tumour progression, early recurrence, and poor prognosis in hepatocellular carcinoma , 2006, The Journal of pathology.

[60]  Wolfgang Jahnke,et al.  Control of Intrinsically Disordered Stathmin by Multisite Phosphorylation* , 2006, Journal of Biological Chemistry.

[61]  Bing Yu,et al.  Silencing stathmin gene expression by survivin promoter-driven siRNA vector to reverse malignant phenotype of tumor cells , 2006, Cancer biology & therapy.

[62]  P. Curmi,et al.  Stathmin Strongly Increases the Minus End Catastrophe Frequency and Induces Rapid Treadmilling of Bovine Brain Microtubules at Steady State in Vitro* , 2006, Journal of Biological Chemistry.

[63]  K. Saito,et al.  Overexpression of stathmin in oral squamous-cell carcinoma: correlation with tumour progression and poor prognosis , 2006, British Journal of Cancer.

[64]  G. Atweh,et al.  Therapeutic interactions between stathmin inhibition and chemotherapeutic agents in prostate cancer , 2006, Molecular Cancer Therapeutics.

[65]  Kristoffer Brännström,et al.  Aneugenic activity of Op18/stathmin is potentiated by the somatic Q18-->e mutation in leukemic cells. , 2006, Molecular biology of the cell.

[66]  J. Ruderman,et al.  Aurora B is required for mitotic chromatin-induced phosphorylation of Op18/Stathmin. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[67]  T. Horie,et al.  Identification of Op18/stathmin as a potential target of ASK1‐p38 MAP kinase cascade , 2006, Journal of cellular physiology.

[68]  G. Atweh,et al.  Synergistic Antiangiogenic Effects of Stathmin Inhibition and Taxol Exposure , 2007, Molecular Cancer Research.

[69]  J. Sung,et al.  Lentivirus‐mediated RNA interference targeting enhancer of zeste homolog 2 inhibits hepatocellular carcinoma growth through down‐regulation of stathmin , 2007, Hepatology.

[70]  Stefanie Kandels-Lewis,et al.  Discrete States of a Protein Interaction Network Govern Interphase and Mitotic Microtubule Dynamics , 2007, PLoS biology.

[71]  M. Steinmetz,et al.  Structure and thermodynamics of the tubulin-stathmin interaction. , 2007, Journal of structural biology.

[72]  P. Schirmacher,et al.  Protumorigenic overexpression of stathmin/Op18 by gain‐of‐function mutation in p53 in human hepatocarcinogenesis , 2007, Hepatology.

[73]  P. Gao,et al.  Inhibiting Proliferation and Enhancing Chemosensitivity to Taxanes in Osteosarcoma Cells by RNA Interference-Mediated Downregulation of Stathmin Expression , 2007, Molecular medicine.

[74]  Y. Miki,et al.  Functional pathway characterized by gene expression analysis of supraclavicular lymph node metastasis-positive breast cancer , 2007, Journal of Human Genetics.

[75]  P. Wen,et al.  The 1p-encoded protein stathmin and resistance of malignant gliomas to nitrosoureas. , 2007, Journal of the National Cancer Institute.

[76]  Mark Gerstein,et al.  The Importance of Bottlenecks in Protein Networks: Correlation with Gene Essentiality and Expression Dynamics , 2007, PLoS Comput. Biol..

[77]  W. Hait,et al.  Silencing of stathmin induces tumor-suppressor function in breast cancer cell lines harboring mutant p53 , 2007, Oncogene.