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

Research output: Contribution to journalArticle

Eun Kyoung Breuer, Daniela Fukushiro-Lopes, Annika Dalheim, Miranda Burnette, Jeremiah Zartman, Simon Kaja, Claire Wells, Loredana Campo, Kimberly J. Curtis, Ricardo Romero-Moreno, Laurie E. Littlepage, Glen L. Niebur, Kent Hoskins, Michael I. Nishimura, Saverio Gentile

Original languageEnglish
Article number180
JournalCell Death and Disease
Volume10
Issue number3
DOIs
Publication statusPublished - 1 Mar 2019

King's Authors

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 suppress the metastatic phenotype in TNBC. This work could represent a paradigm-shifting approach to reducing mortality by targeting a pathway that is central to the development of metastases.

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