Ruan HaiLong, Li Xiang, Yang HongMei, Song ZhengShuai, Tong JunWei, Cao Qi, Wang KeShan, Xiao Wen, Xiao HaiBin, Chen XuanYu, Xu GuangHua, Bao Lin, Xiong ZhiYong, Yuan ChangFei, Liu Lei, Qu Yan, Hu WenJun, Gao YaoYing, Ru ZeYuan, Chen Ke, Zhang XiaoPing
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, Hubei Province, China.
Department of Pathogenic Biology, School of Basic Medicine, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, Hubei Province, China.
Exp Cell Res. 2017 Sep 15;358(2):269-278. doi: 10.1016/j.yexcr.2017.07.004. Epub 2017 Jul 3.
Caveolin-1 (CAV1) has been identified to be up-regulated in many cancers, including clear cell renal cell carcinoma (ccRCC). However, its potential function is still unclear in ccRCC. In this study, we demonstrated that CAV1 was frequently overexpressed in renal cell carcinoma tissues and cells, and was significantly associated with various clinicopathological parameters. In addition, high CAV1 expression was associated with poor disease-free survival (DFS) rate and could serve as a useful diagnostic indicator in ccRCC patients with different clinicopathological stages. Functional experiments demonstrated that CAV1 knockdown inhibited cell migration and invasion, whereas overexpression of CAV1 promoted cell migration and invasion in ccRCC. Moreover, CAV1 expression was up-regulated in sunitinib-resistant renal cancer cell lines, and its overexpression promoted sunitinib resistance. In general, our results confirm that CAV1 plays an important role in the metastasis of kidney cancer and induces sunitinib resistance, so CAV1 function suppression may become a promising clinical treatment strategy during renal cell carcinoma metastasis and sunitinib resistance.
小窝蛋白-1(CAV1)已被证实会在包括肾透明细胞癌(ccRCC)在内的多种癌症中上调。然而,其在ccRCC中的潜在功能仍不清楚。在本研究中,我们证明CAV1在肾细胞癌组织和细胞中经常过度表达,并与各种临床病理参数显著相关。此外,高CAV1表达与无病生存率(DFS)低相关,并且可作为不同临床病理分期的ccRCC患者的有用诊断指标。功能实验表明,敲低CAV1可抑制细胞迁移和侵袭,而CAV1过表达则促进ccRCC中的细胞迁移和侵袭。此外,在对舒尼替尼耐药的肾癌细胞系中CAV1表达上调,并且其过表达促进了对舒尼替尼的耐药性。总体而言,我们的结果证实CAV1在肾癌转移中起重要作用并诱导对舒尼替尼的耐药性,因此抑制CAV1功能可能成为肾细胞癌转移和对舒尼替尼耐药期间一种有前景的临床治疗策略。