Fluid shear stress enhances proliferation of breast cancer cells via downregulation of the c-subunit of the F1FO ATP synthase

Biochem Biophys Res Commun. 2022 Dec 3:632:173-180. doi: 10.1016/j.bbrc.2022.09.084. Epub 2022 Sep 29.

Abstract

The presence of circulating cancer cells in the bloodstream is positively correlated with metastasis. We hypothesize that fluid shear stress (FSS) occurring during circulation alters mitochondrial function, enhancing metastatic behaviors of cancer cells. MCF7 and MDA-MB-231 human breast cancer cells subjected to FSS exponentially increased proliferation. Notably, FSS-treated cells consumed more oxygen but were resistant to uncoupler-mediated ATP loss. We found that exposure to FSS downregulated the F1FO ATP synthase c-subunit and overexpression of the c-subunit arrested cancer cell migration. Approaches that regulate c-subunit abundance may reduce the likelihood of breast cancer metastasis.

Keywords: Breast cancer; F(1)F(O) ATP synthase; Fluid shear stress; Mitochondria.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Cell Proliferation
  • Down-Regulation
  • Female
  • Humans
  • Mitochondrial Proton-Translocating ATPases* / genetics
  • Mitochondrial Proton-Translocating ATPases* / metabolism
  • Oxygen

Substances

  • Mitochondrial Proton-Translocating ATPases
  • Adenosine Triphosphate
  • Oxygen