Department of Urology and Prostate Disease Center, University of Florida College of Medicine, Gainesville, FL, USA.
Oncogene. 2013 Mar 14;32(11):1408-15. doi: 10.1038/onc.2012.161. Epub 2012 May 14.
Incidence of kidney cancer is on the rise, and a better understanding of molecular mechanisms involved in the cancer invasion and metastasis is required for the development of curative therapeutics. In this study, we report that the proinflammatory cytokine prostaglandin E2 (PGE2) induces the malignant SN12C, but not benign HK2 kidney cell invasion. The PGE2 increases SN12C cell invasion through a signal pathway that encompasses EP2 and EP4, Akt, small GTPase RalA and Ral·GTP inactivator RGC2. The results support the idea that targeted interference of EP2/EP4 signal to RalA·GTP may provide benefit to patients diagnosed with advanced kidney cancer.
肾癌发病率呈上升趋势，为了开发有效的治疗方法，需要更好地了解癌症侵袭和转移中涉及的分子机制。在这项研究中，我们报告促炎细胞因子前列腺素 E2（PGE2）可诱导恶性 SN12C 细胞，但不会诱导良性 HK2 肾细胞发生侵袭。PGE2 通过包含 EP2 和 EP4、Akt、小 GTP 酶 RalA 和 Ral·GTP 失活因子 RGC2 的信号通路增加 SN12C 细胞的侵袭。这些结果支持这样一种观点，即靶向干扰 EP2/EP4 信号对 RalA·GTP 的作用可能会使诊断患有晚期肾癌的患者受益。
