Abstract
Signaling adaptor protein Crk regulates cell motility and growth through its targets Dock180 and C3G, those are the guanine-nucleotide exchange factors (GEFs) for small GTPases Rac and Rap, respectively. Recently, overexpression of Crk has been reported in various human cancers. To define the role for Crk in human cancer cells, Crk expression was targeted in the human ovarian cancer cell line MCAS through RNA interference, resulting in the establishment of three Crk knockdown cell lines. These cell lines exhibited disorganized actin fibers, reduced number of focal adhesions, and abolishment of lamellipodia formation. Decreased Rac activity was demonstrated by pull-down assay and FRET-based time-lapse microscopy, in association with suppression of both motility and invasion by phagokinetic track assay and transwell assay in these cells. Furthermore, Crk knockdown cells exhibited slow growth rates in culture and suppressed anchorage-dependent growth in soft agar. Tumor forming potential in nude mice was attenuated, and intraperitoneal dissemination was not observed when Crk knockdown cells were injected into the peritoneal cavity. These results suggest that the Crk is a key component of focal adhesion and involved in cell growth, invasion, and dissemination of human ovarian cancer cell line MCAS.
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References
Albert ML, Kim J-I, Birge RB . (2000). Nat Cell Biol 2: 899–905.
Brugge JS . (1998). Nat Genet 19: 309–311.
Brugnera E, Haney L, Grimsley C, Lu M, Walk SF, Tosello-Trampont AC et al. (2002). Nat Cell Biol 4: 574–582.
Chen Z, Fadiel A, Feng Y, Ohtani K, Rutherford T, Naftolin F . (2001). Cancer 92: 3068–3075.
Feller SM . (2001). Oncogene 20: 6348–6371.
Gotoh T, Hattori S, Nakamura S, Kitayama H, Noda M, Takai Y et al. (1995). Mol Cell Biol 15: 6746–6753.
Gumbiner BM . (1996). Cell 84: 345–357.
Gumienny TL, Brugnera E, Tosello-Trampont AC, Kinchen JM, Haney LB, Nishiwaki K et al. (2001). Cell 107: 27–41.
Hall A . (1998). Science 279: 509–514.
Hasegawa H, Kiyokawa E, Tanaka S, Nagashima K, Gotoh N, Shibuya M et al. (1996). Mol Cell Biol 16: 1770–1776.
Hemmeryckx B, Reichert A, Watanabe M, Kaartinen V, de Jong R, Pattengale PK et al. (2002). Oncogene 21: 3225–3231.
Imaizumi T, Araki K, Miura K, Araki M, Suzuki M, Terasaki H et al. (1999). Biochem Biophys Res Commun 266: 569–574.
Itoh RE, Kurokawa K, Ohba Y, Yoshizaki H, Mochizuki N, Matsuda M . (2002). Mol Cell Biol 22: 6582–6591.
Iwahara T, Akagi T, Shishido T, Hanafusa H . (2003). Oncogene 22: 5946–5957.
Judson PL, He X, Cance WG, Van Le L . (1999). Cancer 86: 1551–1556.
Kiyokawa E, Hashimoto Y, Kobayashi S, Sugimura H, Kurata T, Matsuda M . (1998). Genes Dev 12: 3331–3336.
Lauffenburger DA, Horwitz AF . (1996). Cell 84: 359–369.
Liu E, Thant AA, Kikkawa F, Kurata H, Tanaka S, Nawa A et al. (2000). Cancer Res 60: 2361–2364.
Matsuda M, Reichman CT, Hanafusa H . (1992a). J Virol 66: 115–121.
Matsuda M, Tanaka S, Nagata S, Kojima A, Kurata T, Shibuya M . (1992b). Mol Cell Biol 12: 3482–3489.
Mayer BJ, Hamaguchi M, Hanafusa H . (1988). Nature 332: 272–275.
Miller CT, Chen G, Gharib TG, Wang H, Thomas DG, Misek DE et al. (2003). Oncogene 22: 7950–7957.
Mochizuki N, Ohba Y, Kobayashi S, Otsuka N, Graybiel AM, Tanaka S et al. (2000). J Biol Chem 275: 12667–12671.
Nagashima K, Endo A, Ogita H, Kawana A, Yamagishi A, Kitabatake A et al. (2002). Mol Biol Cell 13: 4231–4242.
Nishihara H, Maeda M, Oda A, Tsuda M, Sawa H, Nagashima K et al. (2002a). Blood 100: 3968–3974.
Nishihara H, Maeda M, Tsuda M, Makino Y, Sawa H, Nagashima K et al. (2002b). Biochem Biophys Res Commun 296: 716–720.
Nishihara H, Tanaka S, Tsuda M, Oikawa S, Maeda M, Shimizu M et al. (2002c). Cancer Lett 180: 55–61.
Ohba Y, Ikuta K, Ogura A, Matsuda J, Mochizuki N, Nagashima K et al. (2001). EMBO J 20: 3333–3341.
O'Neill GM, Fashena SJ, Golemis EA . (2000). Trends Cell Biol 10: 111–119.
Sheetz MP, Felsenfeld DP, Galbraith CG . (1998). Trends Cell Biol 8: 51–54.
Summy JM, Gallick GE . (2003). Cancer Metastasis Rev 22: 337–358.
Takino T, Nakada M, Miyamori H, Yamashita J, Yamada KM, Sato H . (2003). Cancer Res 63: 2335–2337.
Tanaka S, Hanafusa H . (1998). J Biol Chem 273: 1281–1284.
Tanaka S, Hattori S, Kurata T, Nagashima K, Fukui Y, Nakamura S et al. (1993). Mol Cell Biol 13: 4409–4415.
Tanaka S, Morishita T, Hashimoto Y, Hattori S, Nakamura S, Shibuya M et al. (1994). Proc Natl Acad Sci USA 91: 3443–3447.
Tanaka S, Ouchi T, Hanafusa H . (1997). Proc Natl Acad Sci USA 94: 2356–2361.
Tsuda M, Tanaka S, Sawa H, Hanafusa H, Nagashima K . (2002). Cell Growth Differ 13: 131–139.
Yano H, Uchida H, Iwasaki T, Mukai M, Akedo H, Nakamura K et al. (2000). Proc Natl Acad Sci USA 97: 9076–9081.
Acknowledgements
We thank Dr Michiyuki Matsuda (Osaka University, Japan) for setting up a FRET-based time-lapse microscopy and the providing plasmids for monitoring the activity of small GTPases in a single cell. This study was supported in part by the Japan–China Sasakawa Medical Fellowship, by YASUDA Medical Research Foundation, by Grants-in-Aid from the Ministry of Education, Science, Culture, and Sports, and of the Ministry of Health, Labor, and Welfare.
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Linghu, H., Tsuda, M., Makino, Y. et al. Involvement of adaptor protein Crk in malignant feature of human ovarian cancer cell line MCAS. Oncogene 25, 3547–3556 (2006). https://doi.org/10.1038/sj.onc.1209398
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DOI: https://doi.org/10.1038/sj.onc.1209398
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