Journal Article

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

Wang, KeWei, Jia, Linghan, Lu, Min, Guan, Lizhao, Liu, Wen

2015

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adenocarcinoma / Adenocarcinoma - genetics / Adenocarcinoma - pathology / Adenocarcinoma of Lung / Alveoli / Animals / Anoctamin-1 / Apoptosis / Breast cancer / Calcium / Calcium - metabolism / Calcium channels / Calcium chloride / Calcium ions / Cancer / Cancer therapies / Carcinoma / Cell adhesion & migration / Cell cycle / Cell growth / Cell migration / Cell Movement - genetics / Cell proliferation / Cell Proliferation - genetics / Cell size / Chloride / Chloride channels (calcium-gated) / Chloride Channels - biosynthesis / Chloride Channels - genetics / Cholecystokinin / Chromosomes / Colorectal cancer / Drugs / Epithelial cells / Epithelium / Gas exchange / Gene Expression Regulation, Neoplastic / Gene Knockdown Techniques / Homeostasis / Humans / Immunohistochemistry / Inhibition / Kinases / Laboratories / Lung cancer / Lung carcinoma / Lung diseases / Lung Neoplasms - genetics / Lung Neoplasms - pathology / Medical prognosis / Metastasis / Mice / Neck / Neoplasm Invasiveness - genetics / Neoplasm Proteins - biosynthesis / Neoplasm Proteins - genetics / Pharmaceutical sciences / Pharmacology / Proteins / Regulation / Respiratory tract / RNA, Small Interfering - genetics / Squamous cell carcinoma / Tumor cell lines / Tumors / Xenograft Model Antitumor Assays