Cigarette smoke extract induces epithelial-mesenchymal transition of human bladder cancer T24 cells through activation of ERK1/2 pathway.

Abstract

Bladder cancer is a common genitourinary malignant disease worldwide. Abundant evidence has shown that cigarette smoke (CS) is a crucial risk factor for bladder cancer. Nevertheless, the mechanism underlying the relationship between cigarette smoking and bladder cancer remains unclear. In the present study, we investigated the effects of cigarette smoke extract (CSE) on mitogen-activated protein kinase (MAPK) pathway activation and EMT alterations in human bladder cancer T24 cells, and the preventive effect of extracellular regulated protein kinases 1 and 2 (ERK1/2) inhibitor U0126 was further examined. Our results illustrated that CSE exposure induced morphological change of human bladder cancer T24 cells, enhanced migratory and invasive capacities, reduced epithelial marker expression and elevated mesenchymal marker expression. Meanwhile, exposure of T24 cells to CSE resulted in activation of ERK1/2 pathway as well as activator protein 1 (AP-1) proteins. Interestingly, treatment with ERK1/2 inhibitor U0126 effectively abrogated CSE-triggered EMT and ERK1/2/AP-1 activation. These findings provide novel insight into the molecular mechanisms of CS-associated bladder cancer and may open up new avenues in the search for potential target of bladder cancer intervention.

• Authors: Xin Sun, Qifei Deng, Zhaofeng Liang, Zhiqi Liu, Hao Geng, Li Zhao, Qirui Zhou, Jie Liu, Jiaxing Ma, Daming Wang, Dexin Yu, Caiyun Zhong
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 86 Pg. 457-465 (Feb 2017) ISSN: 1950-6007 [Electronic] France
• PMID: 28012925 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Chemical References

• Smoke
• Transcription Factor AP-1

Topics

• Cell Line, Tumor
• Cell Transformation, Neoplastic (chemically induced, genetics)
• Epithelial Cells (drug effects)
• Epithelial-Mesenchymal Transition (drug effects, genetics)
• Gene Expression Regulation, Neoplastic (drug effects, genetics)
• Humans
• MAP Kinase Signaling System (drug effects, genetics)
• Signal Transduction (drug effects, genetics)
• Smoke (adverse effects)
• Smoking (adverse effects)
• Nicotiana (adverse effects)
• Transcription Factor AP-1 (genetics)
• Urinary Bladder Neoplasms (chemically induced, genetics)