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TMEM16A/ANO1 suppression improves response to antibody-mediated targeted therapy of EGFR and HER2/ERBB2
- Source :
- Genes, chromosomescancer. 56(6)
- Publication Year :
- 2016
-
Abstract
- TMEM16A, a Ca2+-activated Cl− channel, contributes to tumor growth in breast cancer and head and neck squamous cell carcinoma (HNSCC). Here, we investigated whether TMEM16A influences the response to EGFR/HER family-targeting biological therapies. Inhibition of TMEM16A Cl− channel activity in breast cancer cells with HER2 amplification induced a loss of viability. Cells resistant to trastuzumab, a monoclonal antibody targeting HER2, showed an increase in TMEM16A expression and heightened sensitivity to Cl− channel inhibition. Treatment of HNSCC cells with cetuximab, a monoclonal antibody targeting EGFR, and simultaneous TMEM16A suppression led to a pronounced loss of viability. Biochemical analyses of cells subjected to TMEM16A inhibitors or expressing chloride-deficient forms of TMEM16A provide further evidence that TMEM16A channel function may play a role in regulating EGFR/HER2 signaling. These data demonstrate that TMEM16A regulates EGFR and HER2 in growth and survival pathways. Furthermore, in the absence of TMEM16A co-targeting, tumor cells may acquire resistance to EGFR/HER inhibitors. Finally, targeting TMEM16A improves response to biological therapies targeting EGFR/HER family members.
- Subjects :
- Receptor, ErbB-2
Squamous Cell Carcinoma of Head and Neck
Chromosomes, Human, Pair 11
Cetuximab
Mice, Nude
Breast Neoplasms
Trastuzumab
Article
Neoplasm Proteins
ErbB Receptors
Mice
Chloride Channels
Head and Neck Neoplasms
Cell Line, Tumor
Carcinoma, Squamous Cell
Animals
Humans
Female
Anoctamin-1
Subjects
Details
- ISSN :
- 10982264
- Volume :
- 56
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Genes, chromosomescancer
- Accession number :
- edsair.pmid..........f2cfffcd36f0872c40245f339e3ed045