Tubulin cofactor A functions as a novel positive regulator of ccRCC progression, invasion and metastasis

• Published in: International journal of cancer 2013-12, Vol.133 (12), p.2801-2811
• Main Authors: Zhang, Peng, Ma, Xin, Song, Erlin, Chen, Weihao, Pang, Haigang, Ni, Dong, Gao, Yu, Fan, Yang, Ding, Qiang, Zhang, Yu, Zhang, Xu
• Format: Article
• Language: English
• Subjects: Apoptosis; Biological and medical sciences; Cancer; Cancer therapies; Carcinoma, Renal Cell - pathology; Cell Cycle; Cell Movement; Cell Proliferation; Cells, Cultured; clear cell renal cell carcinoma; cytoskeleton; Cytoskeleton - metabolism; Disease Progression; Humans; Kidney Neoplasms - pathology; Kidneys; Medical research; Medical sciences; Metastasis; microtubule; Microtubule-Associated Proteins - physiology; Molecular Chaperones - physiology; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Invasiveness; Nephrology. Urinary tract diseases; Polymerization; Rodents; Tubulin - physiology; tubulin cofactor A; Tumors; Tumors of the urinary system
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.28306

Microtubules (Mts), which consist of α/β‐tubulin heterodimers, are involved in cancer development and metastasis. Tubulin cofactor A (TBCA) plays crucial roles in modulating tubulin folding and α/β‐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. What's new? Microtubules—cytoskeletal components consisting of α/β‐tubulin heterodimers—are involved in cancer development and metastasis. While tubulin cofactor A (TBCA) plays crucial roles in modulating tubulin folding and α/β‐tubulin heterodimer polymerization, the function and mechanisms of TBCA in clear cell renal cell carcinoma (ccRCC) remain unclear. Here, Zhang and colleagues observed aberrant expression of TBCA in ccRCC, and revealed its function as a novel positive regulator in ccRCC progression, invasion, and metastasis. Exploration of the mechanisms showed that TBCA could function via modulating cytoskeleton integration and influencing cell cycle progress. TBCA thus emerges as a potential molecul