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Journal Publication
Title of Article OPCML Exerts Antitumor Effects in Cholangiocarcinoma via AXL/STAT3 Inactivation and Rho GTPase Down-regulation 
Date of Acceptance 12 October 2021 
Journal
     Title of Journal Cancer Genomics & Proteomics  
     Standard ISI 
     Institute of Journal International Institute of Anticancer Research 
     ISBN/ISSN  
     Volume 2021 
     Issue 18 
     Month November-December
     Year of Publication 2022 
     Page 771-780 
     Abstract Background/Aim: Opioid-binding protein/cell adhesion molecule-like (OPCML) plays a crucial role in the suppression of tumor progression in several cancer types. Nevertheless, the association between OPCML functions and cholangiocarcinoma (CCA) progression remains unknown. We aimed to investigate biological functions of OPCML and related signaling pathways in CCA cell lines. Materials and Methods: Methylation status and ectopic expression of OPCML were determined in CCA cell lines using methylationspecific polymerase chain reaction and pcDNA3.1+/C- (K)DYK-OPCML, respectively. Cell proliferation, migration and invasion were investigated. Results: OPCML was found to be epigenetically silenced by DNA methylation. Ectopic expression of OPCML inhibited CCA proliferation by inducing apoptosis via AXL receptor tyrosine kinase/signal transducer and activator of transcription 3 (AXL/STAT3) inactivation. It also suppressed cell migration and invasion via downregulation of Rho GTPases, ras homolog family member A (RHOA), Rac family small GTPase 1 (RAC1) and cell division cycle 42 (CDC42). Conclusion: We are the first to unravel the antitumor effects and the related signaling pathways of OPCML in CCA. The loss of OPCML expression due to promoter hypermethylation can cause a decrease in cell death but increase in cell migration and invasion, which may at least in part contribute to CCA progression. 
     Keyword OPCML, methylation, AXL/STAT3 signaling, RHOA/RAC1/CDC42 
Author
577100002-0 Mr. RICUPHAN KHAMKO [Main Author]
Graduate School Doctoral Degree

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