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TMEM207 hinders the tumour suppressor function of WWOX in oral squamous cell carcinoma

Katsuaki Bunai1, Hiroshi Okubo2, Kimika Hano1

  • 1Department of Oral and Maxillofacial Surgery, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.

Journal of Cellular and Molecular Medicine
|November 23, 2017
PubMed

Insights

Aberrant TMEM207 expression promotes oral squamous cell carcinoma (OSCC) progression by disrupting the tumor suppressor WWOX and activating the HIF-1α pathway. This leads to increased aerobic glycolysis and poorer patient prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The WW domain-containing oxidoreductase (WWOX) acts as a tumor suppressor in oral carcinogenesis.
  • Aberrant TMEM207 expression is implicated in tumor progression by potentially interfering with WWOX function.

Purpose of the Study:

  • To investigate TMEM207 expression and its pathobiological role in oral squamous cell carcinoma (OSCC).
  • To explore the regulation of the Hypoxia-Inducible Factor 1-alpha (HIF-1α) pathway by TMEM207 and WWOX in OSCC.

Main Methods:

  • Immunohistochemistry to detect TMEM207 expression in OSCC samples.
  • In situ proximal ligation assay to assess TMEM207 and WWOX colocalization.
  • Xenograft and cell line assays to evaluate the functional impact of TMEM207 expression and knockdown on tumor growth and gene expression.

Main Results:

  • TMEM207 was detected in 40/90 OSCC samples, correlating with lymph node metastasis and poor prognosis.
  • TMEM207 colocalized with WWOX in invasive OSCC cells.
  • TMEM207 overexpression hindered WWOX-HIF-1α binding, increased HIF-1α and GLUT-1 levels, promoted tumor growth, and enhanced aerobic glycolysis.

Conclusions:

  • Aberrant TMEM207 expression contributes to OSCC progression.
  • TMEM207 may promote oral cancer development by disrupting WWOX-mediated regulation of the HIF-1α pathway and enhancing aerobic glycolysis.
Keywords:
WWOXHIF-1αTMEM207Warburg effectaerobic glycosylationoral squamous cell carcinoma

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