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

Jia L, Liu W, Guan L, Lu M, Wang K - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cellular Pharmacology, State Key Laboratory of Natural and Biomimetic Drugs, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.

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.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemical staining of ANO1 protein expression in human lung tissues of benign alveoli adjacent to carcinoma, squamous cell carcinoma and adenocarcinoma.(A) Benign alveoli adjacent to carcinoma showing negative ANO1 staining. (B) Squamous cell lung carcinoma showing negative ANO1 staining. (C) Human lung adenocarcinoma cancer tissue showing ANO1 staining (brown color) of neoplastic epithelium. The scale bar indicates 50 μm.
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pone.0136584.g001: Immunohistochemical staining of ANO1 protein expression in human lung tissues of benign alveoli adjacent to carcinoma, squamous cell carcinoma and adenocarcinoma.(A) Benign alveoli adjacent to carcinoma showing negative ANO1 staining. (B) Squamous cell lung carcinoma showing negative ANO1 staining. (C) Human lung adenocarcinoma cancer tissue showing ANO1 staining (brown color) of neoplastic epithelium. The scale bar indicates 50 μm.

Mentions: To examine the expression level of calcium-activated chloride channel ANO1 proteins, we used ANO1 antibody for immunohistochemical staining and detected ANO1 expression in lung pathologic tissue specimens from 84 patients. As shown in Fig 1, ANO1 protein was highly expressed in adenocarcinoma of lung, whereas tissues from benign alveoli adjacent to carcinoma and squamous cell carcinoma showed negative staining of ANO1. The analysis of immunohistochemical staining revealed that ANO1 protein expression was positive in 34 of 44 (77.3%) human lung adenocarcinoma tissue samples (Table 1). In tissue specimens from squamous cell lung carcinoma, 6 of 40 (15%) were stained ANO1 positive. These results indicate that ANO1 protein is overexpressed in tumorigenesis of human lung cancer and in particular, the lung adenocarcinoma.


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

Jia L, Liu W, Guan L, Lu M, Wang K - PLoS ONE (2015)

Immunohistochemical staining of ANO1 protein expression in human lung tissues of benign alveoli adjacent to carcinoma, squamous cell carcinoma and adenocarcinoma.(A) Benign alveoli adjacent to carcinoma showing negative ANO1 staining. (B) Squamous cell lung carcinoma showing negative ANO1 staining. (C) Human lung adenocarcinoma cancer tissue showing ANO1 staining (brown color) of neoplastic epithelium. The scale bar indicates 50 μm.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4549304&req=5

pone.0136584.g001: Immunohistochemical staining of ANO1 protein expression in human lung tissues of benign alveoli adjacent to carcinoma, squamous cell carcinoma and adenocarcinoma.(A) Benign alveoli adjacent to carcinoma showing negative ANO1 staining. (B) Squamous cell lung carcinoma showing negative ANO1 staining. (C) Human lung adenocarcinoma cancer tissue showing ANO1 staining (brown color) of neoplastic epithelium. The scale bar indicates 50 μm.
Mentions: To examine the expression level of calcium-activated chloride channel ANO1 proteins, we used ANO1 antibody for immunohistochemical staining and detected ANO1 expression in lung pathologic tissue specimens from 84 patients. As shown in Fig 1, ANO1 protein was highly expressed in adenocarcinoma of lung, whereas tissues from benign alveoli adjacent to carcinoma and squamous cell carcinoma showed negative staining of ANO1. The analysis of immunohistochemical staining revealed that ANO1 protein expression was positive in 34 of 44 (77.3%) human lung adenocarcinoma tissue samples (Table 1). In tissue specimens from squamous cell lung carcinoma, 6 of 40 (15%) were stained ANO1 positive. These results indicate that ANO1 protein is overexpressed in tumorigenesis of human lung cancer and in particular, the lung adenocarcinoma.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cellular Pharmacology, State Key Laboratory of Natural and Biomimetic Drugs, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.

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.

No MeSH data available.


Related in: MedlinePlus