Inhibition of the 11q13 amplified calcium activated chloride channel ANO1 reduces Head and Neck and Breast cancer growth
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Britschgi, Adrian, Bill, Anke, Brinkhaus, Heike, Rothwell, Christopher, Clay, Ieuan, Duss, Stephan, Rebhan, Michael, Raman, Pichai, Guy, Chantale, Wetzel, Kristie, George, Elizabeth, Popa, Oana, Lilley, Sarah, Choudhury, Hedaythul, Gosling, Martin, Wang, Louis, Fitzgerald, Stephanie, Borawski, Jason, Baffoe, Jonathan, Labow, Mark, Gaither, Larry and Bentires-Alj, Mohamed (2013) Inhibition of the 11q13 amplified calcium activated chloride channel ANO1 reduces Head and Neck and Breast cancer growth. PNAS, 110 (11). E1026-E1034. ISSN 0027-8424
Abstract
The 11q13 amplicon is one of the most frequently amplified chromosomal regions in human cancer and correlates with poor prognosis1-3. CCDN1, EMS1 and FGF19 have been considered as the main tumor promoting genes contained in this amplicon4,5. Recently, another gene located in the 11q13 amplicon, anoctamin 1 (ANO1, also known as TMEM16A, DOG-1, ORAOV2, TAOS2) was found to be highly expressed in squamous carcinoma of the head & neck (HNSCC), of the esophagus (ESCC), and in GIST6-8. ANO1 has also been shown to be required for head and neck tumor cell growth9. However, the precise role of ANO1, a calcium-activated chloride channel, in tumorigenesis is unknown10-12. Here we introduce ANO1 as a new driver of oncogenesis in HNSCC, ESCC and breast cancer. We found ANO1 to be highly expressed in ~90% of HNSCC, ESCC and ~70% of breast tumors analyzed. Knockdown of ANO1 in HNSCC, ESCC and breast cancer cell lines inhibits proliferation in vitro and in vivo and induces apoptosis by decreasing EGFR-, CAMKII- signaling and subsequently Akt-and ERK-activation. Our results establish an example of the long-sought role of chloride channels in tumorigenesis and provide new insight for oncogenic signaling and therapeutic intervention in HNSCC, ESCC and breast cancer.
| Item Type: | Article |
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| Date Deposited: | 13 Oct 2015 13:14 |
| Last Modified: | 13 Oct 2015 13:14 |
| URI: | https://oak.novartis.com/id/eprint/8198 |