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Caveolin-1-mediated STAT3 activation determines electrotaxis of human lung cancer cells.
Oncotarget 2017; 8(56):95741-95754O

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.

Authors+Show Affiliations

Department of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing 400042, China.Department of Clinical Laboratory, Daping Hospital, Third Military Medical University, Chongqing 400042, China.Department of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing 400042, China.School of Life Sciences, Yunnan Normal University, Kunming 650500, China.School of Life Sciences, Yunnan Normal University, Kunming 650500, China.Department of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing 400042, China.Department of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing 400042, China.Department of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing 400042, China.State Key Laboratory of Trauma, Burns and Combined Injury, Daping Hospital, Third Military Medical University, Chongqing 400042, China.Department of Dermatology, Institute for Regenerative Cures, University of California, Davis, CA 95817, USA.Department of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing 400042, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29221162

Citation

Li, Li, et al. "Caveolin-1-mediated STAT3 Activation Determines Electrotaxis of Human Lung Cancer Cells." Oncotarget, vol. 8, no. 56, 2017, pp. 95741-95754.
Li L, Zhang K, Lu C, et al. Caveolin-1-mediated STAT3 activation determines electrotaxis of human lung cancer cells. Oncotarget. 2017;8(56):95741-95754.
Li, L., Zhang, K., Lu, C., Sun, Q., Zhao, S., Jiao, L., ... He, Y. (2017). Caveolin-1-mediated STAT3 activation determines electrotaxis of human lung cancer cells. Oncotarget, 8(56), pp. 95741-95754. doi:10.18632/oncotarget.21306.
Li L, et al. Caveolin-1-mediated STAT3 Activation Determines Electrotaxis of Human Lung Cancer Cells. Oncotarget. 2017 Nov 10;8(56):95741-95754. PubMed PMID: 29221162.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Caveolin-1-mediated STAT3 activation determines electrotaxis of human lung cancer cells. AU - Li,Li, AU - Zhang,Kejun, AU - Lu,Conghua, AU - Sun,Qin, AU - Zhao,Sanjun, AU - Jiao,Lin, AU - Han,Rui, AU - Lin,Caiyu, AU - Jiang,Jianxin, AU - Zhao,Min, AU - He,Yong, Y1 - 2017/09/28/ PY - 2017/04/11/received PY - 2017/08/26/accepted PY - 2017/12/10/entrez PY - 2017/12/10/pubmed PY - 2017/12/10/medline KW - STAT3 KW - caveolin-1 KW - directional migration KW - electrotaxis KW - lung cancer SP - 95741 EP - 95754 JF - Oncotarget JO - Oncotarget VL - 8 IS - 56 N2 - 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. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/29221162/Caveolin_1_mediated_STAT3_activation_determines_electrotaxis_of_human_lung_cancer_cells_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=21306 DB - PRIME DP - Unbound Medicine ER -