Downregulation of occludin affects the proliferation, apoptosis and metastatic properties of human lung carcinoma

闭合蛋白下调对人肺癌增殖、凋亡和转移特性的影响

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作者:Meifang Wang, Yuquan Liu, Xin Qian, Na Wei, Yijun Tang, Jiong Yang

Abstract

Lung cancer is the most frequent and deadliest cancer in the world, especially in China. However, the molecular mechanisms involved in lung cancer remain unclear. Occludin (OCLN), one of the first identified tight junction proteins, has been revealed to be a necessary integral protein for tight junction structure and function. In the present study, we investigated the role of occludin in lung tumorigenesis. We found that occludin protein expression was highly increased in human lung cancer patient samples. Western blotting results also revealed that occludin expression was different in several lung cancer cell lines, with the highest level in SPC‑A1 cells. Moreover, occludin knockdown inhibited lung cancer cell proliferation in vitro and in vivo. In addition, occludin knockdown promoted the apoptosis of lung cancer cell lines and reduced the invasion ability. Mechanistically, the activity of key growth pathway AKT/PI3K was compromised after occludin knockdown. Expression of apoptosis‑related proteins, BAX, caspase‑3, caspase‑9 and AIF, but not Bcl‑2, were upregulated after silencing of occludin. Collectively, our findings for the first time identify the role of occludin as a tumor promoter and a pro‑metastatic factor in lung cancer, demonstrating that occludin is a potential prognostic biomarker and therapeutic target in lung cancer.

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