PDIA6 promotes the proliferation of HeLa cells through activating the Wnt/β-catenin signaling pathway
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Huijun Gao1,*, Bing Sun2,*, Hailu Fu1, Xinming Chi1, Faming Wang1, Xiaoyu Qi1, Jun Hu1, Shujuan Shao3
1Department of Histology and Embryology, Dalian Medical University, Dalian, China
2Department of Thoracic Surgery, The First Hospital of Dalian Medical University, Dalian, China
3Key Laboratory of Proteomics, Dalian Medical University, Dalian, China
*These authors have contributed equally to this work
Jun Hu, email: email@example.com
Shujuan Shao, email: firstname.lastname@example.org
Keywords: HeLa cell, PDIA6, Wnt signaling pathway, β-catenin phosphorylation, ubiquitylation
Received: January 15, 2016 Accepted: June 29, 2016 Published: July 22, 2016
Protein disulfide isomerase family 6 (PDIA6) belongs to the protein disulfide isomerase (PDI) family, which function as isomerases and molecular chaperones. PDIA6 has recently been shown to promote the proliferation and growth of various types of human cancer cells; however the underlying molecular mechanism remains elusive. Here, we report that PDIA6 enhances the proliferation of HeLa cells through activation of the Wnt/β-catenin signaling pathway. Ectopic overexpression of PDIA6 in HeLa cells led to increased cell proliferation accompanied with accelerated cell cycle progression. Further mechanistic investigation demonstrated that overexpression of PDIA6 resulted in decreased phosphorylation of β-catenin at Ser45 and Ser33/Ser37/Thr41, while increased β-catenin nuclear accumulation, and upregulation of Wnt/ β-catenin signaling target genes cyclinD1 and c-myc, which was abolished by ubiquitin-proteasome inhibitor MG132. These results demonstrated that PDIA6 overexpression promoted the proliferation of HeLa cells by suppressing the phosphorylation of β-catenin, thereby inhibiting the degradation of β-catenin through the ubiquitin-proteasome pathway.
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