Malignant Transformation but Not Normal Cell Growth Depends on Signal Transducer and Activator of Transcription 3

Overview

Journal Cancer Res

Specialty Oncology

Date 2005 Jul 5

PMID 15994959

Citations 59

Authors

Karni Schlessinger

David E Levy

Affiliations

Soon will be listed here.

Abstract

Signal transducer and activator of transcription 3 (STAT3) has been indirectly implicated in numerous fundamental cellular processes, including proliferation, survival, and differentiation. We provide genetic evidence from studies of STAT3-null cells that STAT3 is dispensable for normal growth of mouse fibroblasts in culture. STAT3 contributed to the full induction of some (typified by c-fos) but not all (typified by c-myc) immediate early gene expression, but STAT3-independent processes were sufficient to support full cell growth and survival. However, STAT3 was required to manifest a transformed state following expression of v-src, and STAT3-null cells were impaired for anchorage-independent growth as colonies in soft agar and as tumors in mice. The data suggest that STAT3 mediates the maintenance of focal adhesion kinase activity in the absence of cell adhesion by suppressing the action of an inhibitory phosphatase.

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References

Broome M, Courtneidge S . No requirement for src family kinases for PDGF signaling in fibroblasts expressing SV40 large T antigen. Oncogene. 2000; 19(24):2867-9. DOI: 10.1038/sj.onc.1203608. View

Jones R, Brunton V, Frame M . Adhesion-linked kinases in cancer; emphasis on src, focal adhesion kinase and PI 3-kinase. Eur J Cancer. 2000; 36(13 Spec No):1595-606. DOI: 10.1016/s0959-8049(00)00153-2. View

Blake R, Broome M, Liu X, Wu J, Gishizky M, Sun L . SU6656, a selective src family kinase inhibitor, used to probe growth factor signaling. Mol Cell Biol. 2000; 20(23):9018-27. PMC: 86555. DOI: 10.1128/MCB.20.23.9018-9027.2000. View

Martin G . The hunting of the Src. Nat Rev Mol Cell Biol. 2001; 2(6):467-75. DOI: 10.1038/35073094. View

Bowman T, Broome M, Sinibaldi D, Wharton W, Pledger W, Sedivy J . Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis. Proc Natl Acad Sci U S A. 2001; 98(13):7319-24. PMC: 34666. DOI: 10.1073/pnas.131568898. View

Schaller M . Biochemical signals and biological responses elicited by the focal adhesion kinase. Biochim Biophys Acta. 2001; 1540(1):1-21. DOI: 10.1016/s0167-4889(01)00123-9. View

Carragher N, Westhoff M, Riley D, Potter D, Dutt P, Elce J . v-Src-induced modulation of the calpain-calpastatin proteolytic system regulates transformation. Mol Cell Biol. 2001; 22(1):257-69. PMC: 134206. DOI: 10.1128/MCB.22.1.257-269.2002. View

OShea J, Gadina M, Schreiber R . Cytokine signaling in 2002: new surprises in the Jak/Stat pathway. Cell. 2002; 109 Suppl:S121-31. DOI: 10.1016/s0092-8674(02)00701-8. View

Bromberg J . Stat proteins and oncogenesis. J Clin Invest. 2002; 109(9):1139-42. PMC: 150969. DOI: 10.1172/JCI15617. View

10.

Levy D, Lee C . What does Stat3 do?. J Clin Invest. 2002; 109(9):1143-8. PMC: 150972. DOI: 10.1172/JCI15650. View

11.

Lee C, Raz R, Gimeno R, Gertner R, Wistinghausen B, Takeshita K . STAT3 is a negative regulator of granulopoiesis but is not required for G-CSF-dependent differentiation. Immunity. 2002; 17(1):63-72. DOI: 10.1016/s1074-7613(02)00336-9. View

12.

Niu G, Bowman T, Huang M, Shivers S, Reintgen D, Daud A . Roles of activated Src and Stat3 signaling in melanoma tumor cell growth. Oncogene. 2002; 21(46):7001-10. DOI: 10.1038/sj.onc.1205859. View

13.

Mora L, Buettner R, Seigne J, Diaz J, Ahmad N, Garcia R . Constitutive activation of Stat3 in human prostate tumors and cell lines: direct inhibition of Stat3 signaling induces apoptosis of prostate cancer cells. Cancer Res. 2002; 62(22):6659-66. View

14.

Yang E, Lerner L, Besser D, Darnell Jr J . Independent and cooperative activation of chromosomal c-fos promoter by STAT3. J Biol Chem. 2003; 278(18):15794-9. DOI: 10.1074/jbc.M213073200. View

15.

Chang H, Paulson M, Holko M, Rice C, Williams B, Marie I . Induction of interferon-stimulated gene expression and antiviral responses require protein deacetylase activity. Proc Natl Acad Sci U S A. 2004; 101(26):9578-83. PMC: 470717. DOI: 10.1073/pnas.0400567101. View

16.

Dechow T, Pedranzini L, Leitch A, Leslie K, Gerald W, Linkov I . Requirement of matrix metalloproteinase-9 for the transformation of human mammary epithelial cells by Stat3-C. Proc Natl Acad Sci U S A. 2004; 101(29):10602-7. PMC: 489981. DOI: 10.1073/pnas.0404100101. View

17.

Westhoff M, Serrels B, Fincham V, Frame M, Carragher N . SRC-mediated phosphorylation of focal adhesion kinase couples actin and adhesion dynamics to survival signaling. Mol Cell Biol. 2004; 24(18):8113-33. PMC: 515031. DOI: 10.1128/MCB.24.18.8113-8133.2004. View

18.

Guo W, Giancotti F . Integrin signalling during tumour progression. Nat Rev Mol Cell Biol. 2004; 5(10):816-26. DOI: 10.1038/nrm1490. View

19.

Johnson P, Coussens P, Danko A, Shalloway D . Overexpressed pp60c-src can induce focus formation without complete transformation of NIH 3T3 cells. Mol Cell Biol. 1985; 5(5):1073-83. PMC: 366824. DOI: 10.1128/mcb.5.5.1073-1083.1985. View

20.

Hayes T, Kitchen A, Cochran B . Inducible binding of a factor to the c-fos regulatory region. Proc Natl Acad Sci U S A. 1987; 84(5):1272-6. PMC: 304409. DOI: 10.1073/pnas.84.5.1272. View