HERG channel and cancer: A mechanistic review of carcinogenic processes and therapeutic potential.

Siyi He, Mohamed Taha Moutaoufik, Saadul Islam, Amit Persad, Adam Wu, Khaled A Aly, Humphrey Fonge, Mohan Babu, Francisco S Cayabyab

Journal: Biochimica et biophysica acta. Reviews on cancer 2020;1873(2):188355

PMID: 32135169

Full Text on Elsevier Science View on PubMed

Abstract

The human ether-à-go-go related gene (HERG) encodes the alpha subunit of Kv11.1, which is a voltage-gated K channel protein mainly expressed in heart and brain tissue. HERG plays critical role in cardiac repolarization, and mutations in HERG can cause long QT syndrome. More recently, evidence has emerged that HERG channels are aberrantly expressed in many kinds of cancer cells and play important roles in cancer progression. HERG could therefore be a potential biomarker for cancer and a possible molecular target for anticancer drug design. HERG affects a number of cellular processes, including cell proliferation, apoptosis, angiogenesis and migration, any of which could be affected by dysregulation of HERG. This review provides an overview of available information on HERG channel as it relates to cancer, with focus on the mechanism by which HERG influences cancer progression. Molecular docking attempts suggest two possible protein-protein interactions of HERG with the ß1-integrin receptor and the transcription factor STAT-1 as novel HERG-directed therapeutic targeting which avoids possible cardiotoxicity. The role of epigenetics in regulating HERG channel expression and activity in cancer will also be discussed. Finally, given its inherent extracellular accessibility as an ion channel, we discuss regulatory roles of this molecule in cancer physiology and therapeutic potential. Future research should be directed to explore the possibilities of therapeutic interventions targeting HERG channels while minding possible complications.

Address: Department of Surgery, Neuroscience Research Group, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5, Canada.; Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada.; Department of Medical Imaging, University of Saskatchewan, Saskatoon, Saskatchewan S7N 0W8, Canada; Department of Medical Imaging, Royal University Hospital, Saskatoon, Saskatchewan S7N 0W8, Canada.; Department of Surgery, Neuroscience Research Group, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5, Canada. Electronic address: [email protected].

DOI: 10.1016/j.bbcan.2020.188355