Potassium channel activity controls breast cancer metastasis by affecting β-catenin signaling

Cell Death & Disease
Eun-Kyoung BreuerSaverio Gentile

Abstract

Potassium ion channels are critical in the regulation of cell motility. The acquisition of cell motility is an essential parameter of cancer metastasis. However, the role of K+ channels in cancer metastasis has been poorly studied. High expression of the hG1 gene, which encodes for Kv11.1 channel associates with good prognosis in estrogen receptor-negative breast cancer (BC). We evaluated the efficacy of the Kv11.1 activator NS1643 in arresting metastasis in a triple negative breast cancer (TNBC) mouse model. NS1643 significantly reduces the metastatic spread of breast tumors in vivo by inhibiting cell motility, reprogramming epithelial-mesenchymal transition via attenuation of Wnt/β-catenin signaling and suppressing cancer cell stemness. Our findings provide important information regarding the clinical relevance of potassium ion channel expression in breast tumors and the mechanisms by which potassium channel activity can modulate tumor biology. Findings suggest that Kv11.1 activators may represent a novel therapeutic approach for the treatment of metastatic estrogen receptor-negative BC. Ion channels are critical factor for cell motility but little is known about their role in metastasis. Stimulation of the Kv11.1 channel sup...Continue Reading

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Citations

Oct 9, 2019·Proceedings of the National Academy of Sciences of the United States of America·Yuji AtsutaClifford J Tabin
Nov 5, 2019·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Eun-A KoJae-Hong Ko
May 3, 2019·Journal of Biological Engineering·Qinfeng WuJeremiah J Zartman
Oct 30, 2020·Frontiers in Pharmacology·Raphael Rapetti-MaussOlivier Soriani
Jan 1, 2021·Frontiers in Cell and Developmental Biology·Magdalena BachmannErich Gulbins
Apr 10, 2020·Protein and Peptide Letters·Tsuey Ning SoonYin-Quan Tang
May 1, 2021·International Journal of Molecular Sciences·Silvia MuccioliRoberto Costa
Jun 18, 2021·Advanced Drug Delivery Reviews·Xi HuDaishun Ling
Jul 2, 2021·Frontiers in Cell and Developmental Biology·Xiangchan HouWei Xiong
Nov 26, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Jingyao CuiXin Li

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Methods Mentioned

BETA
xenograft
total hip arthroplasty
nuclear translocation
xenografts
Dispase assay
electrophoresis
confocal microscopy
dissection
Assay

Software Mentioned

KM plotter
Pro Plus
iQ5 Optical System
NIH ImageJ
Mathematica
ImageJ
Image

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