Open AccessTMEM 207 hinders the tumour suppressor function of WWOX in oral squamous cell carcinoma
Author(s) -
Bunai Katsuaki,
Okubo Hiroshi,
Hano Kimika,
Inoue Keisuke,
Kito Yusuke,
Saigo Chiemi,
Shibata Toshiyuki,
Takeuchi Tamotsu
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13456
Subject(s) - wwox , cancer research , gene knockdown , carcinogenesis , suppressor , biology , cancer , colocalization , cell culture , microbiology and biotechnology , genetics
The WW domain‐containing oxidoreductase ( WWOX ) functions as a tumour suppressor in oral carcinogenesis. As aberrant TMEM 207 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 TMEM 207, focusing on the WWOX ‐mediated regulation of the HIF ‐1α pathway in oral squamous cell carcinoma ( OSCC ). TMEM 207 immunoreactivity was detected in 40 of 90 OSCC samples but not in neighbouring non‐tumorous epithelial tissues. Moreover, TMEM 207 expression was significantly correlated with lymph node metastasis and poor prognosis. An in situ proximal ligation assay demonstrated the colocalization of TMEM 207 and WWOX in invasive OSCC cells, especially glycogen‐rich ones. Enforced expression of TMEM 207 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, TMEM 207 knockdown decreased GLUT ‐1 expression in two OSCC cell lines. As a whole, our findings indicate that the aberrant expression of TMEM 207 contributes to tumour progression in OSCC , possibly via promoting aerobic glycolysis.