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Tumor Biology

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01.01.2010 | Research Article

The role of Crk/Dock180/Rac1 pathway in the malignant behavior of human ovarian cancer cell SKOV3

verfasst von: Hui Wang, Hua Linghu, Jin Wang, Ya-ling Che, Ting-xiu Xiang, Wei-xue Tang, Zhen-wei Yao

Erschienen in: Tumor Biology | Ausgabe 1/2010

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Abstract

Small GTPases, particularly the Rho family, are key regulators of cell motility and migration. Dock180 was well known for the main target of signal adaptor protein Crk and acted as a guanine-nucleotide exchange factor for small GTPase Rac1. In the present study, Dock180 was found to combine primarily with CrkI other than CrkII, and its association with Elmo1 was also demonstrated in ovarian cancer cell SKOV3. To evaluate the role of Dock180 in human ovarian cancer cell, we performed RNAi-mediated knockdown of Dock180 in SKOV3 cells using small interfering RNA expression vector. In Dock180 knockdown cells, we found that Elmo1 expression and Rac1 activity were decreased simultaneously. By contrast, the expressions of both another Crk-combining molecule C3G and Rap1 activity were observed to increase obviously. Accordingly, all Dock180 knockdown cells present with evident change in cell morphology, reduced cell proliferation, and attenuated cell migration. Taken together, these results suggest that signal transfer of Crk/Dock180/Rac1 is implicated in actin cytoskeleton reorganization and thus in the cell proliferation, motility, invasion, and of human ovarian cancer cell line SKOV3.

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Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2002;2:563–72.CrossRefPubMed

Hall A. Rho GTPases and the actin cytoskeleton. Science. 1998;279:509–14.CrossRefPubMed

Mayer BJ, Hamaguchi M, Hanafusa H. A novel viral oncogene with structural similarity to phospholipase C.:. Nature. 1988;332(6161):272–5.CrossRefPubMed

Matsuda M, Tanaka S, Nagata S, Kojima A, Kurata T, Shibuya M. Two species of human CRK cDNA encode proteins with distinct biological activities. Mol Cell Biol. 1992;12:3482–9.PubMed

Tanaka S, Hattori S, Kurata T, Nagashima K, Fukui Y, Nakamura S, et al. Both the SH2 and SH3 domains of human CRK protein are required for neuronal differentiation of PC12 cells. Mol Cell Biol. 1993;13:4409–15.PubMed

Gotoh T, Hattori S, Nakamura S, Kitayama H, Noda M, Takai Y, et al. Identification of Rap1 as a target for the Crk SH3 domain-binding guanine nucleotide-releasing factor C3G. Mol Cell Biol. 1995;15(12):6746–53.PubMed

Hasegawa H, Kiyokawa E, Tanaka S, Nagashima K, Gotoh N, Shibuya M, et al. DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane. Mol Cell Biol. 1996;4:1770–6.

Kiyokawa E, Hashimoto Y, Kobayashi S, Sugimura H, Kurata T, Matsuda M. Activation of Rac1 by a Crk SH3-binding protein, DOCK180. Genes Dev. 1998;12:3331–6.CrossRefPubMed

Nishihara H, Tanaka S, Tsuda M, Oikawa S, Maeda M, Shimizu M, et al. Molecular and immunohistochemical analysis of signaling adaptor protein Crk in human cancers. Cancer Lett. 2002;180(1):55–61.CrossRefPubMed

10.

Miller CT, Chen G, Gharib TG, Wang H, Thomas DG, Misek DE, et al. Increased C-CRK proto-oncogene expression is associated with an aggressive phenotype in lung adenocarcinomas. Oncogene. 2003;22(39):7950–7.CrossRefPubMed

11.

Takino T, Nakada M, Miyamori H, Yamashita J, Yamada KM, Sato H. CrkI adapter protein modulates cell migration and invasion in glioblastoma. Cancer Res. 2003;63(9):2335–7.PubMed

12.

Linghu H, Tsuda M, Makino Y, Watanabe T, Ichihara S, Sawa H, et al. Involvement of adaptor protein Crk in malignant feature of human ovarian cancer cell line MCAS. Oncogene. 2006;25:3547–56.CrossRefPubMed

13.

Hasegawa H, Kiyokawa E, Tanaka S, et al. DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane. Mol Cell Biol. 1996;16:1770–6.PubMed

14.

Erickson MR, Galletta BJ, Abmayr SM. Drosophila myoblast city encodes a conserved protein that is essential for myoblast fusion, dorsal closure, and cytoskeletal organization. J Cell Biol. 1997;138:589–603.CrossRefPubMed

15.

Nolan KM, Barrett K, Lu Y, Hu K, Vincent S, Settleman J. Myoblast city, the Drosophila homolog of DOCK180/CED-5, is required in a Rac signaling pathway utilized for multiple developmental processes. Genes Dev. 1998;12:3337–42.CrossRefPubMed

16.

Wu YC, Horvitz HR. C. elegans phagocytosis and cellmigration protein CED-5 is similar to human DOCK180. Nature. 1998;392:501–4.CrossRefPubMed

17.

Gumienny TL, Brugnera E, Tosello-Trampont AC, Kinchen JM, Haney LB, Nishiwaki K. CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. Cell. 2001;107(1):27–41.CrossRefPubMed

18.

Etienne-Manneville S, Hall A. Rho GTPases in cell biology. Nature. 2002;420:629–35.CrossRefPubMed

19.

Para A, Krischke M, Merlot S, Shen Z, Oberholzer M, Lee S, et al. Dictyostelium Dock180-related RacGEFs regulate the actin cytoskeleton during cell motility. Mol Biol Cell. 2009;20(2):699–707.CrossRefPubMed

20.

Lu M, Ravichandran KS. Dock180–ELMO cooperation in Rac activation. Methods Enzymol. 2006;406:388–402.CrossRefPubMed

21.

Grimsley CM, Kinchen JM, Tosello-Trampont A, Brugnera E, Haney LB, Lu M, et al. Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration. J Biol Chem. 2004;279(7):6087–97.CrossRefPubMed

22.

Payne SL, Hendrix MJ, Kirschmann DA. Lysyl oxidase regulates actin filament formation through the p130(Cas)/Crk/DOCK180 signaling complex. J Cell Biochem. 2006;98(4):827–37.CrossRefPubMed

23.

Akakura S, Kar B, Singh S, Cho L, Tibrewal N, Sanokawa-Akakura R, et al. C-terminal SH3 domain of CrkII regulates the assembly and function of the DOCK180/ELMO Rac-GEF. J Cell Physiol. 2005;204(1):344–51.CrossRefPubMed

24.

Gumienny TL, Brugnera E, Tosello-Trampont AC, Kinchen JM, Haney LB, Nishiwaki K, et al. CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway. Is required for phagocytosis and cell migration. Cell. 2001;107(1):27–41.CrossRefPubMed

25.

Brugnera E, Haney L, Grimsley C, Lu M, Walk SF, Tosello-Trampont AC, et al. Unconventional Rac-GEF activity is mediated through the Dock180–ELMO complex. Nat Cell Biol. 2002;4:574–82.PubMed

26.

Albert ML, Kim JI, Birge RB. Alphavbeta5 integrin recruits the CrkII–Dock180–rac1 complex for phagocytosis of apoptotic cells. Nat Cell Biol. 2000;2:899–905.CrossRefPubMed

27.

Hsia DA, Mitra SK, Hauck CR, Streblow DN, Nelson JA, Ilic D, et al. Differential regulation of cell motility and invasion by FAK. Cell Biol. 2003;160(5):753–67.CrossRef

28.

Valle AM, Beuvin M, Boyer B. Activation of Rac1 by Paxillin–Crk–DOCK180 signaling complex is antagonized by Rap1 in migrating NBT-II cells. J Biol Chem. 2004;279(43):44940–6.

29.

Gu J, Sumida Y, Sanzen N, Sekiguchi K. Laminin-10/11 and fibronectin differentially regulate integrin-dependent Rho and Rac activation via p130(Cas)–CrkII–DOCK180 pathway. J Biol Chem. 2001;276(29):27090–7.CrossRefPubMed

30.

Jarzynka MJ, Hu B, Hui KM, Bar-Joseph I, Gu W, Hirose T, et al. ELMO1 and Dock180, a bipartite Rac1 guanine nucleotide exchange factor, promote human glioma cell invasion. Cancer Res. 2007;67(15):7203–11.CrossRefPubMed

31.

Kiyokawa E, Hashimoto Y, Kurata T, Sugimura H, Matsuda M. Evidence that DOCK180 up-regulates signals from the CrkII–p130(Cas) complex. J Biol Chem. 1998;273(38):24479–84.CrossRefPubMed

32.

Tanaka S, Morishita T, Hashimoto Y, Hattori S, Nakamura S, Shibuya M, et al. C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2/ASH proteins. Proc Natl Acad Sci U S A. 1994;91(8):3443–7.CrossRefPubMed

33.

Kitayama H, Sugimoto Y, Matsuzaki T, Ikawa Y, Noda M. A ras-related gene with transformation suppressor activity. Cell. 1989;56(1):77–84.CrossRefPubMed

34.

Van Aelst L, Symons M. Role of Rho family GTPases in epithelial morphogenesis. Genes Dev. 2002;16(9):1032–54.CrossRefPubMed

35.

Bivona TG, Wiener HH, Ahearn IM, Silletti J, Chiu VK, Philips MR. Rap1 up-regulation and activation on plasma membrane regulates T cell adhesion. J Cell Biol. 2004;164(3):461–70.CrossRefPubMed

36.

Larue L, Bellacosa A. Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3′ kinase/AKT pathways. Oncogene. 2005;24(50):7443–54.CrossRefPubMed

Titel: The role of Crk/Dock180/Rac1 pathway in the malignant behavior of human ovarian cancer cell SKOV3
verfasst von: Hui Wang
Hua Linghu
Jin Wang
Ya-ling Che
Ting-xiu Xiang
Wei-xue Tang
Zhen-wei Yao
Publikationsdatum: 01.01.2010
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 1/2010
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-009-0009-9

Springer Medizin

The role of Crk/Dock180/Rac1 pathway in the malignant behavior of human ovarian cancer cell SKOV3

Abstract

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Abstract

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