title: Tubulin cofactor A functions as a novel positive regulator of ccRCC progression, invasion and metastasis.
abstract: 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.
authors.affiliation: Department of Urology, PLA General Hospital, Beijing, People's Republic of China; State Key Laboratory of Kidney Diseases, PLA General Hospital, Beijing, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Erlin
authors.initials: E
authors.lastname: Song
authors.forename: Weihao
authors.initials: W
authors.lastname: Chen
authors.forename: Haigang
authors.initials: H
authors.lastname: Pang
authors.forename: Dong
authors.initials: D
authors.lastname: Ni
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.forename: Yang
authors.initials: Y
authors.lastname: Fan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology*; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D018832:Molecular Chaperones / Q000502:physiology*; D009361:Neoplasm Invasiveness; D014404:Tubulin / Q000502:physiology
chemical_list: D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; C503328:TBCA protein, human; D014404:Tubulin
keywords: cell cycle; clear cell renal cell carcinoma; cytoskeleton; microtubule; tubulin cofactor A