Compression enhances invasive phenotype and matrix degradation of breast Cancer cells via Piezo1 activation

Mingzhi Luo; Grace Cai; Kenneth K Y Ho; Kang Wen; Zhaowen Tong; Linhong Deng; Allen P Liu

doi:10.1186/s12860-021-00401-6

Compression enhances invasive phenotype and matrix degradation of breast Cancer cells via Piezo1 activation

BMC Mol Cell Biol. 2022 Jan 3;23(1):1. doi: 10.1186/s12860-021-00401-6.

Authors

Mingzhi Luo^{1

2}, Grace Cai³, Kenneth K Y Ho^{2

4}, Kang Wen¹, Zhaowen Tong³, Linhong Deng⁵, Allen P Liu^{6

7

8

9

10}

Affiliations

¹ Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu, People's Republic of China.
² Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.
³ Applied Physics Program, University of Michigan, Ann Arbor, MI, USA.
⁴ Present address: Center for Molecular Imaging, Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
⁵ Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu, People's Republic of China. dlh@cczu.edu.cn.
⁶ Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA. allenliu@umich.edu.
⁷ Applied Physics Program, University of Michigan, Ann Arbor, MI, USA. allenliu@umich.edu.
⁸ Department of Biophysics, University of Michigan, Ann Arbor, MI, USA. allenliu@umich.edu.
⁹ Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA. allenliu@umich.edu.
¹⁰ Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI, USA. allenliu@umich.edu.

Abstract

Background: Uncontrolled growth in solid breast cancer generates mechanical compression that may drive the cancer cells into a more invasive phenotype, but little is known about how such compression affects the key events and corresponding regulatory mechanisms associated with invasion of breast cancer cells including cellular behaviors and matrix degradation.

Results: Here we show that compression enhanced invasion and matrix degradation of breast cancer cells. We also identified Piezo1 as the putative mechanosensitive cellular component that transmitted compression to not only enhance the invasive phenotype, but also induce calcium influx and downstream Src signaling. Furthermore, we demonstrated that Piezo1 was mainly localized in caveolae, and both Piezo1 expression and compression-enhanced invasive phenotype of the breast cancer cells were reduced when caveolar integrity was compromised by either knocking down caveolin1 expression or depleting cholesterol content.

Conclusions: Taken together, our data indicate that mechanical compression activates Piezo1 channels to mediate enhanced breast cancer cell invasion, which involves both cellular events and matrix degradation. This may be a critical mechanotransduction pathway during breast cancer metastasis, and thus potentially a novel therapeutic target for the disease.

Keywords: Breast cancer cell; Compression; Invasion; Piezo1.

MeSH terms

Breast Neoplasms*
Female
Humans
Ion Channels* / genetics
Ion Channels* / metabolism
Mechanotransduction, Cellular*
Phenotype
Signal Transduction

Substances

Ion Channels
PIEZO1 protein, human