Oncotarget

Research Papers:

Inhibition of TRPC6 reduces non-small cell lung cancer cell proliferation and invasion

Li-Li Yang, Bing-Chen Liu, Xiao-Yu Lu, Yan Yan, Yu-Jia Zhai, Qing Bao, Paul W. Doetsch, Xingming Deng, Tiffany L. Thai, Abdel A. Alli, Douglas C. Eaton, Bao-Zhong Shen _ and He-Ping Ma

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:5123-5134. https://doi.org/10.18632/oncotarget.14034

Metrics: PDF 1369 views  |   HTML 1155 views  |   ?  


Abstract

Li-Li Yang1,2,3,*, Bing-Chen Liu1,2,3,*, Xiao-Yu Lu3, Yan Yan1,2, Yu-Jia Zhai1,2,3, Qing Bao3, Paul W. Doetsch4, Xingming Deng4, Tiffany L. Thai3,5, Abdel A. Alli3,5, Douglas C. Eaton3,5, Bao-Zhong Shen1,2, He-Ping Ma3,5

1Department of Radiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China

2Molecular Imaging Research Center of Harbin Medical University, Harbin, Heilongjiang, China

3Department of Physiology, Emory University School of Medicine, Atlanta, Georgia, USA

4Department of Radiation Oncology, and Biochemistry and Winship Cancer Institute of Emory University, Atlanta, Georgia, USA

5Center for Cell and Molecular Signaling, Emory University School of Medicine, Atlanta, Georgia, USA

*These authors have contributed equally to this work

Correspondence to:

Bao-Zhong Shen, email: shenbzh@vip.sina.com

He-Ping Ma, email: heping.ma@emory.edu

Keywords: anti-cancer drugs, cell cycle, metastasis, intracellular calcium, confocal microscopy

Received: November 12, 2015     Accepted: November 11, 2016     Published: December 20, 2016

ABSTRACT

Recent studies indicate that the transient receptor potential canonical 6 (TRPC6) channel is highly expressed in several types of cancer cells. However, it remains unclear whether TRPC6 contributes to the malignancy of human non-small cell lung cancer (NSCLC). We used a human NSCLC A549 cell line as a model and found that pharmacological blockade or molecular knockdown of TRPC6 channel inhibited A549 cell proliferation by arresting cell cycle at the S-G2M phase and caused a significant portion of cells detached and rounded-up, but did not induce any types of cell death. Western blot and cell cycle analysis show that the detached round cells at the S-G2M phase expressed more TRPC6 than the still attached polygon cells at the G1 phase. Patch-clamp data also show that TRPC whole-cell currents in the detached cells were significantly higher than in the still attached cells. Inhibition of Ca2+-permeable TRPC6 channels significantly reduced intracellular Ca2+ in A549 cells. Interestingly, either blockade or knockdown of TRPC6 strongly reduced the invasion of this NSCLC cell line and decreased the expression of an adherent protein, fibronectin, and a tight junction protein, zonula occluden protein-1 (ZO-1). These data suggest that TRPC6-mediated elevation of intracellular Ca2+ stimulates NSCLC cell proliferation by promoting cell cycle progression and that inhibition of TRPC6 attenuates cell proliferation and invasion. Therefore, further in vivo studies may lead to a consideration of using a specific TRPC6 blocker as a complement to treat NSCLC.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 14034