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- Title
αB-crystallin complexes with 14-3-3ζ to induce epithelial-mesenchymal transition and resistance to sorafenib in hepatocellular carcinoma.
- Authors
Huang, Xiao-Yong; Ke, Ai-Wu; Shi, Guo-Ming; Zhang, Xin; Zhang, Chi; Shi, Ying-Hong; Wang, Xiao-Ying; Ding, Zhen-Bin; Xiao, Yong-Sheng; Yan, Jun; Qiu, Shuang-Jian; Fan, Jia; Zhou, Jian
- Abstract
The overall survival of patients with hepatocellular carcinoma (HCC) remains poor, and the molecular pathogenesis remains incompletely defined in HCC. Here we report that increased expression of αB-Crystallin in human HCC predicts poor survival and disease recurrence after surgery. Multivariate analysis identifies αB-Crystallin expression as an independent predictor for postoperative recurrence and overall survival. We show that elevated expression of αB-Crystallin promotes HCC progression in vivo and in vitro. We demonstrate that αB-Crystallin overexpression fosters HCC progression by inducing epithelial-mesenchymal transition (EMT) in HCC cells through activation of the extracellular-regulated protein kinase (ERK) cascade, which can counteract the effect of sorafenib. αB-Crystallin complexes with and elevates 14-3-3ζ protein, leading to up-regulation of ERK1/2 activity. Moreover, overexpression of αB-Crystallin in HCC cells induces EMT progression through an ERK1/2/Fra-1/slug signaling pathway. Clinically, our data reveal that overexpression of both αB-Crystallin and 14-3-3ζ correlates with the HCC poorest survival outcomes, and sorafenib response is impaired in patients with αB-Crystallin overexpression.
- Publication
Hepatology (Baltimore, Md.), 2013, Vol 57, Issue 6, p2235
- ISSN
1527-3350
- Publication type
Journal Article
- DOI
10.1002/hep.26255