RRC ID 52480
Author Bunai K, Okubo H, Hano K, Inoue K, Kito Y, Saigo C, Shibata T, Takeuchi T.
Title TMEM207 hinders the tumour suppressor function of WWOX in oral squamous cell carcinoma.
Journal J. Cell. Mol. Med.
Abstract The WW domain-containing oxidoreductase (WWOX) functions as a tumour suppressor in oral carcinogenesis. As aberrant TMEM207 expression may lead to tumour progression by hampering the tumour suppressor function of WWOX in various cancers, we explored the expression and pathobiological properties of TMEM207, focusing on the WWOX-mediated regulation of the HIF-1α pathway in oral squamous cell carcinoma (OSCC). TMEM207 immunoreactivity was detected in 40 of 90 OSCC samples but not in neighbouring non-tumorous epithelial tissues. Moreover, TMEM207 expression was significantly correlated with lymph node metastasis and poor prognosis. An in situ proximal ligation assay demonstrated the colocalization of TMEM207 and WWOX in invasive OSCC cells, especially glycogen-rich ones. Enforced expression of TMEM207 abrogated the binding of WWOX to HIF-1α, increased HIF-1α and GLUT-1 expression, even under normoxic conditions, and promoted tumour growth in a xenoplant assay using SAS tongue squamous cancer cells. In contrast, TMEM207 knockdown decreased GLUT-1 expression in two OSCC cell lines. As a whole, our findings indicate that the aberrant expression of TMEM207 contributes to tumour progression in OSCC, possibly via promoting aerobic glycolysis.
Volume 22(2)
Pages 1026-1033
Published 2018-2
DOI 10.1111/jcmm.13456
PMID 29164763
PMC PMC5783854
MeSH Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism* Carcinoma, Squamous Cell / pathology Carrier Proteins / metabolism* Cell Line, Tumor Disease Progression Down-Regulation / genetics Female Gene Expression Regulation, Neoplastic Gene Silencing Glucose Transporter Type 1 / metabolism Humans Hypoxia-Inducible Factor 1, alpha Subunit / metabolism Male Membrane Proteins / metabolism* Middle Aged Mouth Neoplasms / genetics Mouth Neoplasms / metabolism* Mouth Neoplasms / pathology Neoplasm Invasiveness Prognosis Protein Binding RNA, Small Interfering / metabolism Tumor Suppressor Proteins / metabolism* WW Domain-Containing Oxidoreductase / metabolism* Xenograft Model Antitumor Assays
IF 4.302
Human and Animal Cells SAS(RCB1974)