Tubulin cofactor A functions as a novel positive regulator of ccRCC progression, invasion and metastasis
Tubulin cofactor A functions as a novel positive regulator of ccRCC progression, invasion and metastasis
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微管蛋白辅助因子 A 作为 ccRCC 进展、侵袭和转移的新型正调节因子
DOI：
10.1002/ijc.28306
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发表时间：
2013-12-15
影响因子：
6.4
通讯作者：
Zhang, Xu
中科院分区：
文献类型：
--
作者：
Zhang, Peng;Ma, Xin;Zhang, Xu
微管（Mts）由微管蛋白异二聚体组成，参与癌症的发展和转移。微管蛋白辅因子A（TBCA）在调节微管蛋白折叠和微管蛋白异源二聚体聚合中起关键作用。在这里，我们确定了TBCA在透明细胞肾细胞癌（ccRCC）标本以及细胞系中的异常表达，并揭示了TBCA作为ccRCC进展、侵袭和转移中的新型正调节因子的功能。qRT-PCR、Western blot和免疫组化检测证实，与相应的正常肾组织和HKC相比，TBCA在ccRCC标本和细胞系中显著高表达。因此，通过质粒在ccRCC细胞中过表达和敲低内源性TBCA蛋白水平来检测TBCA对细胞增殖、凋亡和侵袭/迁移的影响。沉默TBCA表达可抑制786-O细胞和Caki-1细胞的增殖，促进786-O细胞的凋亡。下调TBCA表达也降低了786-O细胞的侵袭和迁移能力。有趣的是，TBCA的过表达并没有诱导与TBCA敲低直接相反的生物学特性。更重要的是，机制的探索表明TBCA可以通过调节细胞骨架整合和影响细胞周期进程来发挥作用。下调TBCA在786-O和Caki-1细胞中的表达，可影响细胞骨架的整合和细胞大小，诱导S/G2期细胞阻滞，并导致cyclinA/E和CDK 2的异常表达。通过研究TBCA在调控ccRCC细胞进展、侵袭和转移中的新作用，我们的研究确定TBCA可能是ccRCC治疗的潜在分子靶点。
Microtubules (Mts), which consist of /-tubulin heterodimers, are involved in cancer development and metastasis. Tubulin cofactor A (TBCA) plays crucial roles in modulating tubulin folding and /-tubulin heterodimer polymerization. Here, we identified the aberrant expression of TBCA in clear cell renal cell carcinoma (ccRCC) specimens as well as cell lines and revealed the function of TBCA as a novel positive regulator in ccRCC progression, invasion and metastasis. qRT-PCR, Western blot and immunohistochemistry assays confirmed that TBCA was significantly highly expressed in ccRCC specimens and cell lines compared to their corresponding normal kidney tissues and HKC. Accordingly, the influence of TBCA on cell proliferation, apoptosis and invasion/migration was detected through overexpression and knockdown of endogenous TBCA protein level in ccRCC cells via plasmids. Silencing of TBCA expression inhibited the proliferation of 786-O cells and Caki-1 cells and promoted the apoptosis of 786-O cells. Down-regulation of TBCA expression also reduced the invasion and migration ability of 786-O cells. Interestingly, overexpression of TBCA did not induce biocharacteristics that directly contrasted to those of TBCA knockdown. Importantly, exploration of the mechanism showed that TBCA could function via modulating cytoskeleton integration and influencing cell cycle progress. Furthermore, down-regulation of TBCA expression in 786-O and Caki-1 cells affected cytoskeleton integration and cell size, induced S/G2 cell cycle arrest and led to cyclineA/E and CDK2 aberrant expression. By investigating novel roles of TBCA in regulation of ccRCC cell progression, invasion and metastasis, our study identified that TBCA may be a potential molecular target for ccRCC therapy.