title: PDIA6 promotes the proliferation of HeLa cells through activating the Wnt/β-catenin signaling pathway.
abstract: 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.
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian, China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Thoracic Surgery, The First Hospital of Dalian Medical University, Dalian, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian, China.
authors.forename: Hailu
authors.initials: H
authors.lastname: Fu
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian, China.
authors.forename: Xinming
authors.initials: X
authors.lastname: Chi
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian, China.
authors.forename: Faming
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Qi
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: Key Laboratory of Proteomics, Dalian Medical University, Dalian, China.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Shao
mesh_terms: D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D010766:Phosphorylation; D019704:Protein Disulfide-Isomerases / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D051176:beta Catenin; D019938:Cyclin D1; C496931:PDIA6 protein, human; D019704:Protein Disulfide-Isomerases; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: HeLa cell; PDIA6; Wnt signaling pathway; ubiquitylation; β-catenin phosphorylation