TMEM 207 hinders the tumour suppressor function of WWOX in oral squamous cell carcinoma

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 o...

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Bibliographic Details
Published in:Journal of cellular and molecular medicine 2018-02, Vol.22 (2), p.1026-1033
Main Authors: Bunai, Katsuaki, Okubo, Hiroshi, Hano, Kimika, Inoue, Keisuke, Kito, Yusuke, Saigo, Chiemi, Shibata, Toshiyuki, Takeuchi, Tamotsu
Format: Article
Language:English
Subjects:
Carcinogenesis
Glycogen
Glycolysis
Hypoxia-inducible factor 1a
Immunoreactivity
Invasiveness
Lymph nodes
Metastases
Oral cancer
Oral squamous cell carcinoma
Oxidoreductase
Squamous cell carcinoma
Tissues
Tongue
Tumors
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Summary: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.
ISSN:1582-1838
1582-4934
DOI:10.1111/jcmm.13456