PLCγ is required for RhoGDI2-mediated cisplatin resistance in gastric cancer
PLCγ is required for RhoGDI2-mediated cisplatin resistance in gastric cancer
复制标题
DOI：
10.1016/j.bbrc.2011.09.121
复制
发表时间：
2011-10-28
影响因子：
3.1
通讯作者：
Yoo, Jiyun
中科院分区：
文献类型：
--
作者：
Cho, Hee Jun;Baek, Kyoung Eun;Yoo, Jiyun
Rho GDP解离抑制剂2（RhoGDI 2）是Rho家族GTP酶的调节剂。我们实验室最近的研究表明，RhoGDI 2表达可能增强顺铂的耐药性，并促进胃癌的肿瘤生长和恶性进展。在这项研究中，我们证明，磷脂酶C-γ（PLC γ）是所需的RhoGDI 2介导的顺铂耐药和胃癌细胞的侵袭。磷酸化PLC γ的水平在RhoGDI 2过表达的SNU-484细胞中显著增强，相比之下，在RhoGDI 2耗尽的MKN-28细胞中被抑制。PLC γ表达的缺失或其活性的抑制不仅显着增加顺铂诱导的细胞凋亡，而且还抑制RhoGDI 2过表达SNU-484细胞的侵袭能力。综上所述，我们的研究结果表明，PLC γ在RhoGDI 2介导的顺铂耐药和胃癌细胞的细胞侵袭中起着关键作用。(C)2011 Elsevier Inc. All rights reserved.
Rho GDP dissociation inhibitor 2 (RhoGDI2) is a regulator of the Rho family GTPases. Recent work from our laboratory suggests that RhoGDI2 expression potentially enhances resistance to cisplatin as well as promotes tumor growth and malignant progression in gastric cancer. In this study, we demonstrate that phospholipase C-gamma (PLC gamma) is required for RhoGDI2-mediated cisplatin resistance and cancer cell invasion in gastric cancer. The levels of phosphorylated PLC gamma are markedly enhanced in RhoGDI2 -overexpressing SNU-484 cells and, by contrast, repressed in RhoGDI2-depleted MKN-28 cells. Depletion of PLC gamma expression or inhibition of its activity not only significantly increases cisplatin-induced apoptosis but also suppresses the invasive ability of RhoGDI2-overexpressing SNU-484 cells. Taken together, our results suggest that PLC gamma plays a key role in RhoGDI2-mediated cisplatin resistance and cell invasion in gastric cancer cells. (C) 2011 Elsevier Inc. All rights reserved.