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CD151通过激活肾细胞癌中的TGF-β1/Smad信号通路促进细胞转移。

CD151 promotes cell metastasis via activating TGF-β1/Smad signaling in renal cell carcinoma.

作者信息

Yu Yajie, Liang Chao, Wang Shangqian, Zhu Jundong, Miao Chenkui, Hua Yibo, Bao Meiling, Cao Qiang, Qin Chao, Shao Pengfei, Wang Zengjun

机构信息

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

出版信息

Oncotarget. 2018 Jan 8;9(17):13313-13323. doi: 10.18632/oncotarget.24028. eCollection 2018 Mar 2.

Abstract

Tetraspanin CD151 has been identified as a tumor promoter, which is upregulated in various malignant cell types. However, the function of CD151 and its underlying mechanism in renal cell carcinoma is still unknown. In this study, we detected the expression of CD151 in RCC cells and tissues and explored its regulatory mechanism. We found that CD151 was upregulated in renal cell carcinoma tissues and cells and its expression was significantly associated with tumor stage (p=0.019) and survival (p=0.001) by analyzing tissue microarrays. After silencing of CD151 via lentivirus vector in Caki-1 and Caki-2 cells, reduced ability of migration and invasion were detected with downregulation of CD151. The opposite results were observed in cells with CD151 overexpression. Furthermore, western blotting was performed to investigate the influence of CD151 on epithelial-to-mesenchymal transition, matrix metalloproteinase 9 and TGF-β1/Smad signaling pathway in RCC. Subsequently, upregulating the protein level of transforming growth factor-β1 in cells with silencing of CD151 could rescue the malignant behaviors inhibited, which indicated that CD151 may play its promoting role in RCC partially by stimulating the expression of TGF-β1. Conclusively, CD151 might exhibit a prominent role in migration and invasion of RCC cells via activating TGF-β1/Smad signaling pathway.

摘要

四跨膜蛋白CD151已被确定为一种肿瘤促进因子,在多种恶性细胞类型中上调。然而,CD151在肾细胞癌中的功能及其潜在机制仍不清楚。在本研究中,我们检测了CD151在肾细胞癌细胞和组织中的表达,并探讨了其调控机制。通过分析组织芯片,我们发现CD151在肾细胞癌组织和细胞中上调,其表达与肿瘤分期(p=0.019)和生存率(p=0.001)显著相关。在Caki-1和Caki-2细胞中通过慢病毒载体沉默CD151后,检测到迁移和侵袭能力降低,同时CD151表达下调。在CD151过表达的细胞中观察到相反的结果。此外,进行蛋白质印迹分析以研究CD151对肾细胞癌上皮-间质转化、基质金属蛋白酶9和TGF-β1/Smad信号通路的影响。随后,在沉默CD151的细胞中上调转化生长因子-β1的蛋白水平可以挽救被抑制的恶性行为,这表明CD151可能部分通过刺激TGF-β1的表达在肾细胞癌中发挥其促进作用。总之,CD151可能通过激活TGF-β1/Smad信号通路在肾细胞癌细胞的迁移和侵袭中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5f8/5862580/d64143ad8bd8/oncotarget-09-13313-g001.jpg

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