Li Muhan, Pei Xuelian, Wang Guoliang, Zhan Jun, Du Juan, Jiang Hao, Tang Yan, Zhang Hongquan, He Huiying
Key Laboratory of Carcinogenesis and Translational Research, Μinistry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, P.R. China.
Department of Urology, Peking University Third Hospital, Beijing 100083, P.R. China.
Oncol Rep. 2017 Sep;38(3):1551-1560. doi: 10.3892/or.2017.5789. Epub 2017 Jul 4.
Kindlin‑2 is an integrin-interacting, FERM-domain containing protein, which plays a critical role in tumor progression. However, the specific role of Kindlin‑2 in renal cell carcinoma (RCC) progression has not been described. In this study we investigated the role of Kindlin‑2 in progression of clear cell RCC (CCRCC), which is the most common RCC subtype, and its underlying mechanisms. Immunohistochemistry studies show that expression of Kindlin‑2 in CCRCC is positively correlated with tumor grade, and Kindlin‑2 expression in advanced CCRCC with lymph node metastasis was greater than in localized CCRCC. Kindlin‑2 expression in CCRCC tumor specimens is also correlated with short patient survival, but is not an independent prognostic factor. Kindlin‑2 promotes CCRCC cell migration and invasion in vitro, whereas knockdown of Kindlin‑2 inhibited cell migration and invasion. Knockdown of Kindlin‑2 also inhibits ACHN cell proliferation in vitro and tumorigenesis in vivo. Kindlin‑2 may be required for Wnt pathway activation which underlies the mechanisms of Kindlin‑2 promoting CCRCC progression. These findings demonstrate that expression of Kindlin‑2 is associated with tumor grade, lymph node metastasis and poor prognosis in CCRCC patients. Kindlin‑2 may regulate CCRCC progression through the Wnt signaling pathway, promoting CCRCC cell proliferation, migration and invasion.
黏着斑蛋白2是一种与整合素相互作用、含有FERM结构域的蛋白质，在肿瘤进展中起关键作用。然而，黏着斑蛋白2在肾细胞癌（RCC）进展中的具体作用尚未见报道。在本研究中，我们调查了黏着斑蛋白2在透明细胞RCC（CCRCC，最常见的RCC亚型）进展中的作用及其潜在机制。免疫组织化学研究表明，CCRCC中黏着斑蛋白2的表达与肿瘤分级呈正相关，且伴有淋巴结转移的晚期CCRCC中黏着斑蛋白2的表达高于局限性CCRCC。CCRCC肿瘤标本中黏着斑蛋白2的表达也与患者生存期短相关，但不是独立的预后因素。黏着斑蛋白2在体外促进CCRCC细胞迁移和侵袭，而敲低黏着斑蛋白2则抑制细胞迁移和侵袭。敲低黏着斑蛋白2还在体外抑制ACHN细胞增殖并在体内抑制肿瘤发生。Wnt通路激活可能是黏着斑蛋白2促进CCRCC进展机制的基础，而这可能需要黏着斑蛋白2的参与。这些发现表明，黏着斑蛋白2的表达与CCRCC患者的肿瘤分级、淋巴结转移及预后不良相关。黏着斑蛋白2可能通过Wnt信号通路调节CCRCC进展，促进CCRCC细胞增殖、迁移和侵袭。
