Σάββατο 19 Μαΐου 2018

Role of LKB1 in migration and invasion of Cr(VI)-transformed human bronchial epithelial Beas-2B cells

Hexavalent chromium [Cr(VI)] is a common human carcinogen associated with lung cancer and other pulmonary diseases as exposure to excessive Cr(VI) induces malignant transformation in human lung epithelial cells. The mechanism underlying its carcinogenicity is unclear in terms of how it facilitates metastases. Cr(VI) compounds are reported to briefly promote cell migration in a concentration-dependent manner and oncogene liver kinase B1 (LKB1) was reduced in Cr(VI)-transformed cells. Overexpression of LKB1 in Beas-2B-Cr [Cr(VI) malignantly transformed Beas-2B cells] suppressed cell migration and invasion and inactivated FAK, Src, MMP-2, GSK3β, β-catenin, and HEF1, which contribute to cell migration and invasion. Silencing LKB1 with siRNA promoted migration and invasion, and activated these downstream proteins. Long-term exposure to Cr(VI) enhanced the migration and invasiveness of Beas-2B cells and reduced the expression of LKB1, while activating these proteins as mentioned above. Data suggest that LKB1 may regulate downstream proteins such as FAK, Src, MMP-2, GSK3β, β-catenin, and HEF1, and affect the migration and invasiveness of Beas-2B-Cr cells. * Jian Lu and Zhongping Zhou contributed equally to the writing of this article. Correspondence to Jian Lu, PhD, Jiangsu University, No.301, Xuefu Road, Jingkou District, Zhenjiang, Jiangsu 212013, China Tel: +86 511 8878 8776; fax: +86 511 8879 1923; e-mail: lujian@ujs.edu.cn Correspondence to Zhanao Wu, MS, No. 359 Hospital, No.8, Zhongshan East Road, Zhenjiang, Jiangsu 212050, China Tel/fax: +86 511 8333 5901; e-mail: wza_007@qq.com Received November 10, 2017 Accepted April 9, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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