2. Academic Validation
  3. Potassium channel activity controls breast cancer metastasis by affecting β-catenin signaling

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

  • Cell Death Dis. 2019 Feb 21;10(3):180. doi: 10.1038/s41419-019-1429-0.
Eun-Kyoung Breuer 1,  Daniela Fukushiro-Lopes 2,  Annika Dalheim 3,  Miranda Burnette 4,  Jeremiah Zartman 4,  Simon Kaja 2 5 6,  Claire Wells 7,  Loredana Campo 1,  Kimberly J Curtis 8,  Ricardo Romero-Moreno 8,  Laurie E Littlepage 8,  Glen L Niebur 8 9,  Kent Hoskins 10,  Michael I Nishimura 3,  Saverio Gentile 11 12
Affiliations

Affiliations

  • 1 Department of Radiation Oncology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, 60153, USA.
  • 2 Department of Molecular Pharmacology & Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, 60153, USA.
  • 3 Department of Surgery, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, 60153, USA.
  • 4 Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN, 46556, USA.
  • 5 Department of Ophthalmology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA.
  • 6 Research Service, Edward Hines Jr. VA Hospital, Hines, IL, USA.
  • 7 Division of Cancer Studies, King's College London, Rm. 2.34 A New Hunts House, Guy's Campus, London, SE1 1 UL, UK.
  • 8 Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN, 46556, USA.
  • 9 Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN, 46556, USA.
  • 10 Division of Hematology Oncology, Department of Medicine, University of Illinois Chicago, Chicago, IL, 60612, USA.
  • 11 Department of Molecular Pharmacology & Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, 60153, USA. sgentile@uic.edu.
  • 12 Division of Hematology Oncology, Department of Medicine, University of Illinois Chicago, Chicago, IL, 60612, USA. sgentile@uic.edu.
PMID: 30792401 DOI: 10.1038/s41419-019-1429-0
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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