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, Yong He

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)95741-95754
Number of pages14
JournalOncotarget
Volume8
Issue number56
DOIs
StatePublished - 2017

    Fingerprint

Keywords

  • Caveolin-1
  • Directional migration
  • Electrotaxis
  • Lung cancer
  • STAT3

ASJC Scopus subject areas

  • Oncology

Cite this

Li, L., Zhang, K., Lu, C., Sun, Q., Zhao, S., Jiao, L., Han, R., Lin, C., Jiang, J., Zhao, M., & He, Y. (2017). Caveolin-1-mediated STAT3 activation determines electrotaxis of human lung cancer cells. Oncotarget, 8(56), 95741-95754. https://doi.org/10.18632/oncotarget.21306