Oncotarget

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This article has been corrected. Correction in: Oncotarget. 2018; 9:28291.

Caveolin-1-mediated STAT3 activation determines electrotaxis of human lung cancer cells

Li Li, Kejun Zhang, Conghua Lu, Qin Sun, Sanjun Zhao, Lin Jiao, Rui Han, Caiyu Lin, Jianxin Jiang, Min Zhao and Yong He _

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Oncotarget. 2017; 8:95741-95754. https://doi.org/10.18632/oncotarget.21306

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Abstract

Li Li1, Kejun Zhang2, Conghua Lu1, Qin Sun3, Sanjun Zhao3, Lin Jiao1, Rui Han1, Caiyu Lin1, Jianxin Jiang4, Min Zhao5 and Yong He1

1Department of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing 400042, China

2Department of Clinical Laboratory, Daping Hospital, Third Military Medical University, Chongqing 400042, China

3School of Life Sciences, Yunnan Normal University, Kunming 650500, China

4State Key Laboratory of Trauma, Burns and Combined Injury, Daping Hospital, Third Military Medical University, Chongqing 400042, China

5Department of Dermatology, Institute for Regenerative Cures, University of California, Davis, CA 95817, USA

Correspondence to:

Yong He, email: heyong@dphospital.tmmu.edu.cn, heyong8998@126.com

Keywords: electrotaxis; lung cancer; directional migration; caveolin-1; STAT3

Received: April 11, 2017    Accepted: August 26, 2017    Published: September 28, 2017

ABSTRACT

Migration of cancer cells leads to the invasion of distant organs by primary tumors. Further, endogenous electric fields (EFs) in the tumor microenvironment direct the migration of lung cancer cells by a process referred to as electrotaxis – although the precise mechanism remains unclear. Caveolin-1 (Cav-1) is a multifunctional scaffolding protein that is associated with directional cell migration and lung cancer invasion; however, its precise role in lung cancer electrotaxis is unknown. In the present study, we first detected outward electric currents on the tumor body surface in lung cancer xenografts using a highly-sensitive vibrating probe. Next, we found that highly-metastatic H1650-M3 cells migrated directionally to the cathode. In addition, reversal of the EF polarity reversed the direction of migration. Mechanistically, EFs activated Cav-1 and the downstream signaling molecule STAT3. RNA interference of Cav-1 reduced directional cell migration, which was accompanied by dampened STAT3 activation. Furthermore, pharmacological inhibition of STAT3 significantly reduced the electrotactic response, while rescue of STAT3 activation in Cav-1 knock-down cells restored electrotaxis. Taken together, these results suggest that endogenous EFs in the tumor micro-environment might play an important role in lung cancer metastasis by guiding cell migration through a Cav-1/STAT3-mediated signaling pathway.


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