Inhibition of Calcium-Activated Chloride Channel ANO1/TMEM16A Suppresses Tumor Growth and Invasion in Human Lung Cancer

Abstract

Lung cancer or pulmonary carcinoma is primarily derived from epithelial cells that are thin and line on the alveolar surfaces of the lung for gas exchange. ANO1/TMEM16A, initially identified from airway epithelial cells, is a member of Ca2+-activated Cl- channels (CaCCs) that function to regulate epithelial secretion and cell volume for maintenance of ion and tissue homeostasis. ANO1/TMEM16A has recently been shown to be highly expressed in several epithelium originated carcinomas. However, the role of ANO1 in lung cancer remains unknown. In this study, we show that inhibition of calcium-activated chloride channel ANO1/TMEM16A suppresses tumor growth and invasion in human lung cancer. ANO1 is upregulated in different human lung cancer cell lines. Knocking-down ANO1 by small hairpin RNAs inhibited proliferation, migration and invasion of GLC82 and NCI-H520 cancel cells evaluated by CCK-8, would-healing, transwell and 3D soft agar assays. ANO1 protein is overexpressed in 77.3% cases of human lung adenocarcinoma tissues detected by immunohistochemistry. Furthermore, the tumor growth in nude mice implanted with GLC82 cells was significantly suppressed by ANO1 silencing. Taken together, our findings provide evidence that ANO1 overexpression contributes to tumor growth and invasion of lung cancer; and suppressing ANO1 overexpression may have therapeutic potential in lung cancer therapy.

Inhibition of ANO1 by luteolin and its cytotoxicity in human prostate cancer PC-3 cells

“…ANO1/TMEM16A, a calcium-activated chloride channel (CaCC), has been shown to be highly amplified in several human cancers and recent evidence suggests ANO1 as a potential therapeutic target for cancer because down regulation of ANO1 reveals therapeutic advantages on HNSCC, breast, prostate and lung cancer treatment [6, 8, 9, 22]. In the present study, we performed a cell-based screening to identify novel ANO1 inhibitor from natural products and revealed luteolin as a bona fide inhibitor of ANO1.…”

Expression Profiling of a Human Thyroid Cell Line Stably Expressing the BRAFV600E Mutation

“…ANO1-induced cell proliferation and tumor growth were accompanied by an CANCER GENOMICS & PROTEOMICS 14: 53-68 (2017) 64 increase in ERK1/2 activation and cyclin D1 induction (32). In lung cancer and colorectal cancer, ANO1 overexpression was related to tumor growth and invasion (33,34). The SERPINE2 gene encodes a member of the serpine protein family that inhibits serine proteases.…”

Copy number gain of 11q13.3 genes associates with pathological stage in hypopharyngeal squamous cell carcinoma

“…(Britschgi et al, 2013;Bill et al, 2015), but may also directly engage with MAP kinase pathways to promote growth and survival (Duvvuri et al, 2012;Sui et al, 2014). Although it is often reported in association with metastasis and recurrence in translational studies, other studies have reported effects on proliferation and local invasion (Ruiz et al, 2012;Shiwarski et al, 2014;Jia et al, 2015), suggesting the tumourigenic functions of Ano1 may be more complex than a 'grow to go' switch.…”