title: Piezo1 forms mechanosensitive ion channels in the human MCF-7 breast cancer cell line.
abstract: Mechanical interaction between cells - specifically distortion of tensional homeostasis-emerged as an important aspect of breast cancer genesis and progression. We investigated the biophysical characteristics of mechanosensitive ion channels (MSCs) in the malignant MCF-7 breast cancer cell line. MSCs turned out to be the most abundant ion channel species and could be activated by negative pressure at the outer side of the cell membrane in a saturable manner. Assessing single channel conductance (GΛ) for different monovalent cations revealed an increase in the succession: Li(+) < Na(+) < K(+) ≈Rb(+) ≈ Cs(+). Divalent cations permeated also with the order: Ca(2+) < Ba(2+). Comparison of biophysical properties enabled us to identify MSCs in MCF-7 as ion channels formed by the Piezo1 protein. Using patch clamp technique no functional MSCs were observed in the benign MCF-10A mammary epithelial cell line. Blocking of MSCs by GsMTx-4 resulted in decreased motility of MCF-7, but not of MCF-10A cells, underscoring a possible role of Piezo1 in invasion and metastatic propagation. The role of Piezo1 in biology and progression of breast cancer is further substantiated by markedly reduced overall survival in patients with increased Piezo1 mRNA levels in the primary tumor.
authors: Department of Biophysics, Medical University of Graz, Graz, Austria.
authors: Chouyang
authors: C
authors: Li
authors: Department of Biophysics, Medical University of Graz, Graz, Austria.
authors: Simin
authors: S
authors: Rezania
authors: Department of Biophysics, Medical University of Graz, Graz, Austria.
authors: Sarah
authors: S
authors: Kammerer
authors: Department of Biophysics, Medical University of Graz, Graz, Austria.
authors: Armin
authors: A
authors: Sokolowski
authors: Department of Biophysics, Medical University of Graz, Graz, Austria.
authors: Trevor
authors: T
authors: Devaney
authors: Department of Biophysics, Medical University of Graz, Graz, Austria.
authors: Astrid
authors: A
authors: Gorischek
authors: Department of Pathology, Medical University of Graz, Graz, Austria.
authors: Stephan
authors: S
authors: Jahn
authors: Division of Bioinformatics, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
authors: Hubert
authors: H
authors: Hackl
authors: Department of Biophysics, Medical University of Graz, Graz, Austria.
authors: Klaus
authors: K
authors: Groschner
authors: Department of Human Genetics, Medical University of Graz, Graz, Austria.
authors: Christian
authors: C
authors: Windpassinger
authors: Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.
authors: Ernst
authors: E
authors: Malle
authors: Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors: Thomas
authors: T
authors: Bauernhofer
authors: Department of Biophysics, Medical University of Graz, Graz, Austria.
authors: Wolfgang
authors: W
authors: Schreibmayer
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D017136:Ion Transport / Q000235:genetics; D061986:MCF-7 Cells; D040542:Mechanotransduction, Cellular; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D007473:Ion Channels; D009363:Neoplasm Proteins; C515204:PIEZO1 protein, human