Emerging roles for multifunctional ion channel auxiliary subunits in cancer

TY - JOUR

T1 - Emerging roles for multifunctional ion channel auxiliary subunits in cancer

AU - Haworth, Alexander

AU - Brackenbury, William John

N1 - © 2019 The Authors. Published by Elsevier Ltd.

PY - 2019/6

Y1 - 2019/6

N2 - Several superfamilies of plasma membrane channels which regulate transmembrane ion flux have also been shown to regulate a multitude of cellular processes, including proliferation and migration. Ion channels are typically multimeric complexes consisting of conducting subunits and auxiliary, non-conducting subunits. Auxiliary subunits modulate the function of conducting subunits and have putative non-conducting roles, further expanding the repertoire of cellular processes governed by ion channel complexes to processes such as transcellular adhesion and gene transcription. Given this expansive influence of ion channels on cellular behaviour it is perhaps no surprise that aberrant ion channel expression is a common occurrence in cancer. This review will focus on the conducting and non-conducting roles of the auxiliary subunits of various Ca2+, K+, Na+ and Cl- channels and the burgeoning evidence linking such auxiliary subunits to cancer. Several subunits are upregulated (e.g. Cavβ, Cavγ) and downregulated (e.g. Kvβ) in cancer, while other subunits have been functionally implicated as oncogenes (e.g. Navβ1, Cavα2δ1) and tumour suppressor genes (e.g. CLCA2, KCNE2, BKγ1) based on in vivo studies. The strengthening link between ion channel auxiliary subunits and cancer has exposed these subunits as potential biomarkers and therapeutic targets. However further mechanistic understanding is required into how these subunits contribute to tumour progression before their therapeutic potential can be fully realised.

AB - Several superfamilies of plasma membrane channels which regulate transmembrane ion flux have also been shown to regulate a multitude of cellular processes, including proliferation and migration. Ion channels are typically multimeric complexes consisting of conducting subunits and auxiliary, non-conducting subunits. Auxiliary subunits modulate the function of conducting subunits and have putative non-conducting roles, further expanding the repertoire of cellular processes governed by ion channel complexes to processes such as transcellular adhesion and gene transcription. Given this expansive influence of ion channels on cellular behaviour it is perhaps no surprise that aberrant ion channel expression is a common occurrence in cancer. This review will focus on the conducting and non-conducting roles of the auxiliary subunits of various Ca2+, K+, Na+ and Cl- channels and the burgeoning evidence linking such auxiliary subunits to cancer. Several subunits are upregulated (e.g. Cavβ, Cavγ) and downregulated (e.g. Kvβ) in cancer, while other subunits have been functionally implicated as oncogenes (e.g. Navβ1, Cavα2δ1) and tumour suppressor genes (e.g. CLCA2, KCNE2, BKγ1) based on in vivo studies. The strengthening link between ion channel auxiliary subunits and cancer has exposed these subunits as potential biomarkers and therapeutic targets. However further mechanistic understanding is required into how these subunits contribute to tumour progression before their therapeutic potential can be fully realised.

KW - Auxiliary subunit

KW - Calcium channel

KW - Cancer

KW - Chloride channel

KW - Potassium channel

KW - Sodium channel

UR - http://www.scopus.com/inward/record.url?scp=85065080699&partnerID=8YFLogxK

U2 - 10.1016/j.ceca.2019.04.005

DO - 10.1016/j.ceca.2019.04.005

M3 - Review article

C2 - 31071485

SN - 0143-4160

VL - 80

SP - 125

EP - 140

JO - Cell calcium

JF - Cell calcium

ER -