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Multiomics Analysis of TMEM200A as a Pan-Cancer Biomarker
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TMEM16A induces MAPK and contributes directly to tumorigenesis and cancer progression

Umamaheswar Duvvuri1, Daniel J Shiwarski, Dong Xiao

  • 1Department of Otolaryngology, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine and Magee-Women's Research Institute, Pittsburgh, Pennsylvania 15213, USA. duvvuriu@upmc.edu

Cancer Research
|May 9, 2012
PubMed

Insights

The calcium channel TMEM16A is overexpressed in head and neck cancers, promoting tumor growth via the ERK pathway. Inhibiting TMEM16A may offer a new cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Gene amplification of TMEM16A (ANO1) is frequent in malignancies.
  • TMEM16A's role in human tumorigenesis remains unstudied.

Purpose of the Study:

  • To investigate the functional role of TMEM16A in tumor growth.
  • To elucidate the mechanisms underlying TMEM16A-mediated tumorigenesis.

Main Methods:

  • Assessed TMEM16A expression in head and neck squamous cell carcinoma (SCCHN).
  • Evaluated TMEM16A's effect on cell proliferation, anchorage-independent growth, and tumor growth in vitro and in vivo.
  • Investigated the involvement of the ERK/MAPK pathway and cyclin D1.
  • Tested a TMEM16A inhibitor (T16A-inh01).

Main Results:

  • TMEM16A was overexpressed in 80% of SCCHN, correlating with poor survival.
  • TMEM16A overexpression promoted tumor growth and proliferation.
  • TMEM16A-induced growth involved ERK1/2 activation and cyclin D1 induction.
  • Inhibiting MEK/ERK or TMEM16A abrogated tumor growth.

Conclusions:

  • TMEM16A plays a functional role in SCCHN tumorigenesis.
  • The ERK/MAPK pathway is critical for TMEM16A-mediated proliferation.
  • TMEM16A is a potential therapeutic target for SCCHN and other cancers.

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