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VEGF‐C mediates RhoGDI2‐induced gastric cancer cell metastasis and cisplatin resistance
Author(s) -
Jun Cho Hee,
Kim InKyu,
Park SunMi,
Eun Baek Kyoung,
Nam InKoo,
Park SeungHo,
Ryu KiJun,
Choi Jungil,
Ryu Jinhyun,
Hong SoonChan,
Jeong SangHo,
Lee YoungJoon,
Ko GyungHyuck,
Won Kim Jae,
Won Lee Chang,
Soo Kang Sang,
Yoo Jiyun
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28801
Subject(s) - cisplatin , cancer research , metastasis , cancer , rac1 , cancer cell , cell migration , biology , apoptosis , cell , cell culture , medicine , chemotherapy , microbiology and biotechnology , signal transduction , biochemistry , genetics
Rho GDP dissociation inhibitor 2 (RhoGDI2) expression is correlated with tumor growth, metastasis and chemoresistance in gastric cancer. However, the mechanisms by which RhoGDI2 promotes tumor cell survival and metastasis remain unclear. In this study, we clearly demonstrate that RhoGDI2 upregulates VEGF‐C expression and RhoGDI2 expression is positively correlated with VEGF‐C expression in human gastric tumor tissues as well as parental gastric cancer cell lines. VEGF‐C depletion suppressed RhoGDI2‐induced gastric cancer metastasis and sensitized RhoGDI2‐overexpressing cells to cisplatin‐induced apoptosis in vitro and in vivo . Secreted VEGF‐C enhanced gastric cancer cell invasion and conferred cisplatin resistance to RhoGDI2‐overexpressing cells. We also show that RhoGDI2 positively regulates Rac1 activity in gastric cancer cells. Inhibition of Rac1 expression suppressed RhoGDI2‐induced VEGF‐C expression, and this inhibition was associated with decreased invasiveness and increased sensitivity to cisplatin in RhoGDI2‐overexpressing cells. Our results indicate that RhoGDI2 might be a potential therapeutic target for simultaneously reducing metastasis risk and enhancing chemotherapy efficacy in gastric cancer.