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Effects of TMEM16A Expression on Motility and Metastasis in Epithelial Tumor Cells
Author(s) -
Shiwarski Daniel John,
He Lu Mei,
Huang Xin,
Gollin Suzanne,
Grandis Jennifer,
Duvvuri Umamaheswar
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.610.12
Subject(s) - motility , metastasis , cancer research , cell culture , cancer , cancer cell , primary tumor , cell , biology , medicine , microbiology and biotechnology , genetics
TMEM16A, a novel gene that regulates Ca + ‐activated Cl − currents, was recently isolated from oral cavity cancer cells. TMEM16A is overexpressed in several tumor types; however, the role that TMEM16A plays in promoting tumor motility remains unclear. The goal of this project was to characterize the role of TMEM16A in cancer cell motility, invasion, and metastasis. We hypothesized that TMEM16A contributed to tumor cell motility and may be an important factor in metastasis through epithelial to mesenchymal transition (EMT) in cancer. SCCHN and T24 bladder cancer cell lines were transduced with lentiviral particles encoding RNAi against TMEM16A, and stable cell lines overexpressing TMEM16A were also created. To assess motility we used trans‐well migration and scratch assays with agonists and inhibitors of TMEM16A. As hypothesized, overexpression of TMEM16A decreased motility and these results were confirmed using a dominant inactive construct. We further evaluated TMEM16A levels in primary and metastatic cell lines. Metastatic lines had reduced TMEM16A levels compared to paired primary cell lines. In summary, our results provide novel insights into the biologic function of TMEM16A in tumor motility and metastasis. This research has significantly enhanced our understanding about the pathogenesis of epithelial tumors, and can potentially be translated to many cancer types. Funded by: SPORE H&N Career Development Award (U.D.) Department of Otolaryngology Startup Funds (U.D.) SPORE H&N P50 CA 0A097190