STAT5a activation mediates the epithelial to mesenchymal transition induced by oncogenic RhoA

Molecular Biology of the Cell

Volumn 14, Issue 1, 2003, Pages 40-53

  Benitah, Salvador Aznar ^a   Valerón, Pilar F ^a   Rui, Hallgeir ^b   Lacal, Juan Carlos ^a  

^a INSTITUTO DE INVESTIGACIONES BIOMÉDICAS ALBERTO SOLS   (Spain)

^b UNIFORMED SERVICES UNIVERSITY OF THE HEALTH SCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; GUANOSINE TRIPHOSPHATASE; LYSOPHOSPHATIDIC ACID; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN SERINE KINASE; RHO FACTOR; SERINE; STAT5 PROTEIN; STAT5A PROTEIN; STRESS ACTIVATED PROTEIN KINASE; SYNAPTOPHYSIN; TRANSCRIPTION FACTOR; TYROSINE; UNCLASSIFIED DRUG; UVOMORULIN; VIMENTIN;

ANIMAL CELL; ARTICLE; CELL MOTILITY; CONTROLLED STUDY; DEPHOSPHORYLATION; DNA BINDING; DOWN REGULATION; ENZYME ACTIVATION; EPITHELIUM; GENE CONTROL; GENE IDENTIFICATION; HUMAN; HUMAN CELL; MESENCHYME; MUTAGENESIS; NONHUMAN; PHOSPHORYLATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION;

DNA-BINDING PROTEINS; EPITHELIUM; GENE EXPRESSION REGULATION; HUMANS; JANUS KINASE 2; MESODERM; MILK PROTEINS; PHOSPHORYLATION; PROLACTIN; PROMOTER REGIONS (GENETICS); PROTEIN-TYROSINE KINASES; PROTO-ONCOGENE PROTEINS; RHOA GTP-BINDING PROTEIN; STAT5 TRANSCRIPTION FACTOR; TRANS-ACTIVATORS; TRANSCRIPTION, GENETIC;

ANIMALIA;

EID: 0037243197     PISSN: 10591524     EISSN: None     Source Type: Journal    
DOI: 10.1091/mbc.E02-08-0454     Document Type: Article

References (73)

1. Abraham, M.T., Kuriakose, M.A., Sacks, P.G., Yee, H., Chiriboga, L., Bearer, E.L., and Delacure, M.D. (2001). Motility-related proteins as markers for head and neck squamous cell cancer. Laryngoscope 111, 1285-1289.
2. Alberts, A.S., Geneste, O., and Treisman, R. (1998). Activation of SRF-regulated chromosomal templates by Rho-family GTPases requires a signal that also induces H4 hyperacetylation. Cell 92, 475-487.
3. Al-Shami, A., Mahanna, W., and Naccache, P.H. (1998). Granulocyte-macrophage colony-stimulating factor-activated signaling pathways in human neutrophils: selective activation of Jak2, Stat3, and Stat5b. J. Biol. Chem. 273, 1058-1063.
4. Aznar, S., and Lacal, J.C. (2001a). Searching new targets for anticancer drug design: the families of Ras and RhoGTPases and their effectors. Prog. Nucleic Acid Res. Mol. Biol. 67, 193-234.
5. Aznar, S., and Lacal, J.C. (2001b). Rho signals to cell growth and apoptosis. Cancer Lett. 165, 1-10.
6. Aznar, S., Valeron, P.F., del Rincon, S.V., Perez, L.F., Perona, R., and Lacal, J.C. (2001). Simultaneous tyrosine and serine phosphorylation of stat3 transcription factor is involved in rho a GTPase oncogenic transformation. Mol. Biol. Cell 12, 3282-3294.
7. Bakin, A.V, Tomlinson, A.K., Bhowmick, N.A., Moses, H.L., and Arteaga, C.L. (2000). Phosphatidylinositol 3-kinase function is required for transforming growth factor beta-mediated epithelial to mesenchymal transition, and cell migration. J. Biol. Chem. 275, 36803-36810.
8. Ballestero, R.P., Esteve, P., Perona, R., Jiménez, B., and Lacal, J.C. (1991). Biological function of Aplysia californica rho gene: the superfamily of ras related genes. NATO Advanced Science Institute Series, A220, 237-242.
9. Bar-Sagi, D., and Hall, A. (2000). Ras and Rho GTPases: a family reunion. Cell 103, 227-238.
10. Beadling, C., Ng, J., Babbage, J.W., and Cantrell, D.A. (1996). Interleukin-2 activation of STAT5 requires the convergent action of tyrosine kinases and a serine/threonine kinase pathway distinct from the Raf1/ERK2 MAP kinase pathway. EMBO J. 15, 1902-1913.
11. Bhowmick, N.A., Ghiassi, M., Bakin, A., Aakre, M., Lundquist, C.A., Engel, M.E., Arteaga, C.L., and Moses, H.L. (2001). Transforming growth factor-betal mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism. Mol. Biol. Cell 12, 27-36.
12. Boccaccio, C., Ando, M., Tamagnone, L., Bardelli, A., Michieli, P., Battistini, C., and Comoglio, P.M. (1998). Induction of epithelial tubules by growth factor HGF depends on the STAT pathway. Nature 391, 285-288.
13. Bourdoulous, S., Orend, G., MacKenna, D.A., Pasqualini, R., and Ruoslahti, E. (1998). Fibronectin matrix regulates activation of RHO and CDC42 GTPases and cell cycle progression. J. Cell Biol. 143, 267-276.
14. Charron, F., Tsimiklis, G., Arcand, M., Robitaille, L., Liang, Q., Molkentin, J.D., Meloche, S., and Nemer, M. (2001). Tissue-specific GATA factors are transcriptional effectors of the small GTPase RhoA. Genes Dev. 15, 2702-2719.
15. Chen, J., Sadowski, H.B., Kohanski, R.A., and Wang, L.H. (1997). Stat5 is a physiological substrate of the insulin receptor. Proc. Natl. Acad. Sci. USA 94, 2295-2300.
16. Clark, E.A., Golub, T.R., Lander, E.S., and Hynes, R.O. (2000). Genomic analysis of metastasis reveals an essential role for RhoC. Nature 406, 532-535.
17. Danen, E.H., Sonneveld, P., Sonnenberg, A., and Yamada, K.M. (2000). Dual stimulation of Ras/mitogen-activated protein kinase and RhoA by cell adhesion to fibronectin supports growth factorstimulated cell cycle progression. J. Cell Biol. 151, 1413-1422.
18. Dang, J., Boyd, D., Wang, H., Allgayer, H., Doe, W.F., and Wang, Y. (1999). A region between -141 and -61 containing a proximal AP-1 is essential for constitutive expression of urokinase-type plasminogen activator receptor. Eur. J. Biochem. 264, 92-99.
19. Darnell, J.E., Jr. (1997). STATs and gene regulation. Science 277, 1630-1635.
20. Davud, M., Wong, L., Flavell, R., Thompson, S.A., Wells, A., Larner, A.C., and Johnson, G.R. (1996). STAT activation by epidermal growth factor (EGF) and amphiregulin: requirement for the EGF receptor kinase but not for tyrosine phosphorylation sites or JAK1. J. Biol. Chem. 271, 9185-9188.
21. Decker, T., and Kovarik, P. (2000). Serine phosphorylation of STATs. Oncogene 19, 2628-2637.
22. del Peso, L., Hernandez-Alcoceba, R., Embade, N., Carnero, A., Esteve, P., Paje, C., and Lacal, J.C. (1997). Rho proteins induce metastatic properties in vivo. Oncogene 15, 3047-3057.
23. Delarue, F.L., Taylor, B.S., and Sebti, S.M. (2001). Ras and Rho suppress whereas RhoB enhances cytokine-induced transcription of nitric oxide synthase-2 in human normal liver AKN-1 cells and lung cancer A-549 cells. Oncogene 20, 6531-6537.
24. Evers, E.E., Zondag, G.C., Malliri, A., Price, L.S., ten Klooster, J.P., van der Kammen, R.A., and Collard, J.G. (2000) Rho family proteins in cell adhesion and cell migration. Eur. J. Cancer 36, 1269-1274.
25. Faruqi, T.R., Gomez, D., Bustelo, X.R., Bar-Sagi, D., and Reich, N.C. (2001). Racl mediates Stat3 activation by autocrine IL-6. Proc. Natl. Acad. Sci. USA 98, 9014-9019.
26. Gouilleux, F., Wakao, H., Mundt, M., and Groner, B. (1994). Prolactin induces phosphorylation of Tyr694 of Stat5 (MGF), a prerequisite for DNA binding and induction of transcription. EMBO J. 13, 4361-4369.
27. Grimley, P.M., Dong, F., and Rui, H. (1999). Stat5a and Stat5b: fraternal twins of signal transduction and transcriptional activation. Cytokine Growth Factor Rev. 10, 131-157.
28. Groner, B., Fritsche, M., Stocklin, E., Berchtold, S., Merkle, C., Moriggi, R., and Pfitzner, E. (2000). Regulation of the trans-activation potential of STAT5 through its DNA-binding activity and interaction with heterologous transcription factors. Growth Horm. IGF Res. 10(suppl B), S15-S20.
29. Hill, C.S., Wynne, J., and Treisman, R. (1995). The Rho family GTPases RhoA, Racl, and CDC42Hs regulate transcriptional activation by SRF. Cell 81, 1159-1170.
30. Kaartinen, V., Haataja, L., Nagy, A., Heisterkamp, N., and Groffen, J. (2002). TGFbeta3-induced activation of RhoA/Rho-kinase pathway is necessary but not sufficient for epithelio-mesenchymal transdifferentiation: implications for palatogenesis. Int. J. Mol. Med. 9, 563-570.
31. Kamai, T., Arai, K., Tsujii, T., Honda, M., and Yoshida, K. (2001). Overexpression of RhoA mRNA is associated with advanced stage in testicular germ cell tumor. BJU Int. 87, 227-231.
32. Keely, P.J. (2001). Rho GTPases as early markers for tumor progression. Lancet 358, 1744-1745.
33. Kirken, R.A., Malabarba, M.G., Xu, J., DaSilva, L., Erwin, R.A., Liu, X., Hennighausen, L., Rui, H., and Farrar, W.L. (1997). Two discrete regions of interleukin-2 (IL-2) receptor beta independently mediate IL2 activation of a PD98059/rapamycin/wortmannin-insensitive Stat5a/b serine kinase. J. Biol. Chem. 272, 15459-15465.
34. Levy, D.E., and Gilliland, D.G. (2000). Divergent roles of STAT1 and STAT5 in malignancy as revealed by gene disruptions in mice. Oncogene. 19, 2505-2510.
35. Marinissen, M.J., Chiariello, M., and Gutkind, S. (2001). Regulation of gene expression by the small GTPase Rho through the ERK6 (p38γ) MAP kinase pathway. Genes Dev. 15, 535-553.
36. Matsumoto, Y., Tanaka, K., Harimaya, K., Nakatani, F., Matsuda, S., and Iwamoto, Y. (2001). Small GTP-binding protein Rho both increased and decreased cellular motility, activation of matrix metalloproteinase 2, and invasion of human osteosarcoma cells. Jpn. J. Cancer Res. 92, 429-438.
37. Meinke, A., Barahmand-Pour, F., Wohrl, S., Stoiber, D., and Decker, T. (1996). Activation of different Stat5 isoforms contributes to celltype-restricted signaling in response to interferons. Mol. Cell. Biol. 16, 6937-6944.
38. Mira, J.P., Benard, V., Groffen, J., Sanders, L.C., and Kanus, U.G. (2000). Endogenous, hyperactive Rac3 controls proliferation of breast cancer cells by a p21-activated kinase-dependent pathway. Proc. Natl. Acad. Sci. USA 97, 185-189.
39. Montaner, S., Perona, R., Saniger, L., and Lacal, J.C. (1998). Multiple signaling pathways lead to the activation of the nuclear factor kB by the Rho family of GTPases. J. Biol. Chem. 273, 12779-12785.
40. Montaner, S., Perona, R., Saniger, L., and Lacal, J.C. (1999). Activation of serum response factor by RhoA is mediated by the nuclear factor-kB and C/EBP transcription factors. J. Biol. Chem. 274, 8506-8515.
41. Muller, S.M., Okan, E., and Jones, P. (2000). Regulation of urokinase receptor transcription by Ras- and Rho-family GTPases. Biochem. Biophys. Res. Commun. 270, 892-898.
42. Park, S.H., Yanashita, H., Rui, H., and Waxman, D.J. (2001). Serine phosphorylation of GH-activated signal transducer, and activator of transcription 5a (STAT5a), and Stat5b: impact on Stat5 transcriptional activity. Mol. Endocrinol. 15, 2157-2171.
43. Perona, R., Esteve, P., Jimenez, B., Ballestero, R.P., Ramon y Cajal, S., and Lacal, J.C. (1993). Tumorigenic activity of rho genes from Aplysia californica. Oncogene 8, 1285-1292.
44. Perona, R., Montaner, S., Saniger, L., Sanchez-Perez, I., Bravo, R., and Lacal, J.C. (1997). Activation of nuclear factor-κB by Rho, CDC42, and Rac-1 proteins. Genes Dev. 11, 463-475.
45. Psichari, E., Balmain, A., Plows, D., Zoumpourlis, V., and Pintzas, A. (2002). High activity of serum response factor in the mesenchymal transition of epithelial tumor cells is regulated by RhoA signaling. J. Biol. Chem. 277, 29490-29495.
46. Ridley, A.J. (2001). Rho family proteins: coordinating cell responses. Trends Cell Biol. 11, 471-477.
47. Rosen, R.L., Winestock, K.D., Chen, G., Liu, X., Hennighausen, L., and Finbloom, D.S. (1996). Granulocyte-macrophage colony-stimulating factor preferentially activates the 94-kD STAT5A and an 80-kD STAT5A isoform in human peripheral blood monocytes. Blood 88, 1206-1214.
48. Sahai, E., Alberts, A.S., and Treisman, R. (1998). RhoA effector mutants reveal distinct effector pathways for cytoskeletal reorganization, SRF activation and transformation. EMBO J. 17, 1350-1361.
49. Sahai, E., and Marshall, C.J. (2002). Rock and Dia have opposing effects on adherens junctions downstream of Rho. Nat. Cell Biol. 4, 408-415.
50. Schuringa, J.J., Dekker, L.V., Vellenga, E., and Kruijer, W. (2001). Sequential activation of Racl, SEK-1/MKK4, and protein kinase C delta is required for interleukin-6-induced STAT3 Ser-727 phosphorylation and transactivation. J. Biol. Chem. 276, 27709-27715.
51. Schuringa, J.J., Jonk, L.J., Dokter, W.H., Vellenga, E., and Kruijer, W. (2000). Interleukin-6-induced STAT3 transactivation and Ser727 phosphorylation involves Vav, Rac-1, and the kinase SEK-1/MKK-4 as signal transduction components. Biochem. J. 347, 89-96.
52. Shuai, K., Schindler, C., Prezioso, V.R., and Darnell, J.E., Jr. (1992). Activation of transcription by IFN gamma: tyrosine phosphorylation of a 91 kDa DNA binding protein. Science 259, 1808-1812.
53. Simon, A.R., Vikis, H.G., Stewart, S., Fanburg, B.L., Cochran, B.H., and Guan, K.L. (2000). Regulation of STAT3 by direct binding to the Racl GTPase. Science 290, 144-147.
54. Sotiropoulos, A., Gineitis, D., Copeland, J., and Treisman, R. (1999). Signal-regulated activation of serum response factor is mediated by changes in actin dynamic. Cell 98, 159-169.
55. Stahl, N., Farruggella, T., Boulton, T.G., Zhong, Z., Darnell, J.E., Jr., and Yancopoulos, G.D. (1995). Choice of STATs and other substrates specified by modular tyrosine-based motifs in cytokine receptors. Science 267, 1349-1352.
56. Takamura, M., Sakamoto, M., Genda, T., Ichida, T., Asakura, H., and Hirohashi, S. (2001). Inhibition of intrahepatic metastasis of human hepatocellular carcinoma by Rho-associated protein kinase inhibitor Y-27632. Hepatology 33, 577-581.
57. Takemoto, H., Doki, Y., Shiozaki, H., Imamura, H., Utsunomiya, T., Miyata, H., Yano, M., Inoue, M., Fujiwara, Y., and Minden, M. (2001) Localization of IQGAP1 is inversely correlated with intracellular adhesion mediated by E-cadherin in gastric cancers. Int. J. Cancer 91, 783-788.
58. Valgeirsdottir, S., Oaukku, K., Silvermoinen, O., Heldin, C.H., and Claesson-Welsh, L. (1998). Activation of Stat5 by platelet-derived growth factor (PDGF) is dependent on phosphorylation sites in PDGF beta-receptor juxtamembrane and kinase insert domains. Oncogene 16, 505-515.
59. Van Aelst, L., and D'Souza-Schorey, C. (1997). RhoGTPases and signaling network. Genes Dev. 11, 2295-2322.
60. Van Golen, K.L., Wu, Z.F., Qiao, X.T., Bao, L., and Merajver, S.D. (2000a). RhoC GTPase overexpression modulates induction of angiogenic factors in breast cells. Neoplasia 2, 418-425.
61. Van Golen, K.L., Wu, Z.F., Qiao, X.T., Bao, L., and Merajver, S.D. (2000b). RhoC GTPase, a novel transforming oncogene for human mammary epithelial cells that partially recapitulates the inflammatory breast cancer phenotype. Cancer Res. 60, 5832-5838.
62. Wang, Y., Dang, J., Wang, H., Allgayer, H., Murrell, G.A., and Boyd, D. (2000). Identification of a novel factor-kappa B sequence involved in expression of urokinase-type plasminogen activator receptor. Eur. J. Biochem. 267, 3248-3254.
63. Welsh, C.F., Roovers, K., Villanueva, J., Liu, Y., Schwartz, M.A., and Assoian, R.K. (2001). Timing of cyclin D1 expression within G1 phase is controlled by Rho. Nat. Cell Biol. 3, 950-957.
64. Wen, Z., and Darnell, J.E., Jr. (1997). Mapping of Stat3 serine phosphorylation to a single residue (727) and evidence that serine phosphorylation has no influence on DNA binding of Stat1 and Stat3. Nucleic Acids Res. 24, 2062-2067.
65. Wen, Z., Zhong, Z., and Darnell, J.E., Jr. (1995). Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell 82, 241-250.
66. Westwick, J.K., Lambert, Q.T., Clarck, G.J., Symons, M., Van Aelst, L., Pestell, R.G., and Der, C.J. (1997). Rac regulation of transformation, gene expression, and actin organization by multiple, PAK-independent pathways. Mol. Cell Biol. 17, 1324-1335.
67. Whitehead, I.P., Lambert, Q.T., Glaven, J.A., Abe, K., Rossman, K.L., Mahon, G.M., Trzaskos, J.M., Kay, R., Campbell, S.L., and Der, C.J. (1999). Dependence of Dbl and Dbs transformation on MEK and NF-kB activation. Mol. Cell Biol. 19, 7759-7770.
68. Yamashita, H., Nevalainen, M.T., Xu, J., LeBaron, M.J., Wagner, K.U., Erwin, R.A., Harmon, J.M., Hennighausen, L., Kirken, R.A., and Rui, H. (2001). Role of serine phosphorylation of Stat5a in prolactin-stimulated beta-casein gene expression. Mol. Cell. Endocrinol. 183, 151-163.
69. Yamashita, H., Xu, J., Erwin, R.A., Rarrar, W.L., Kirken, R.A., and Rui, H. (1998). Differential control of the phosphorylation state of proline-juxtaposed serine residues Ser725 of Stat5a and Ser730 of Stat5b in prolactin-sensitive cells. J. Biol. Chem. 273, 3021-3024.
70. Yu, C.L., Jove, R., and Burakoff, S.J. (1997). Constitutive activation of the Janus kinase-STAT pathway in T lymphoma overexpressing the Lck protein tyrosine kinase. J. Immunol. 159, 5206-5210.
71. Zhong, C., Kinch, M.S., and Burridge, K. (1997). Rho-stimulated contractility contributes to the fibroblastic phenotype of Ras-transformed epithelial cells. Mol. Biol. Cell 8, 2329-2344.
72. Zohar, M., Teramoto, H., Katz, B.Z., Yamada, K.M., and Gutkind, J.S. (1998). Effector domain mutants of Rho dissociated cytoskeletal changes from nuclear signaling and cellular transformation. Oncogene 17, 991-998.
73. Zondag, G.C., Evers, E.E., ten Klooster, J.P., van der Krammen, R.A., and Collard, J.G. (2000). Oncogenic Ras downregulates Rac activity, which leads to increased Rho activity and epithelial-mesenchymal transition. J. Cell Biol. 149, 775-782.