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Updated: Jan 25, 2026
Author Spotlight: Exploring the Role of Ion Channels in Cancer: Characterization and Potential Treatment Approaches
Published on: June 16, 2023
Emerging roles for multifunctional ion channel auxiliary subunits in cancer
Alexander S Haworth1, William J Brackenbury1
1Department of Biology, University of York, Heslington, York, YO10 5DD, UK; York Biomedical Research Institute, University of York, Heslington, York, YO10 5DD, UK.
Abstract:
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.
Insights
Ion channel auxiliary subunits regulate cell processes and are increasingly linked to cancer. Aberrant expression of these subunits suggests they are potential cancer biomarkers and therapeutic targets.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Plasma membrane channels regulate ion flux, impacting cell proliferation and migration.
- Ion channels are complexes of conducting and auxiliary subunits, with auxiliary subunits modulating function and influencing adhesion and transcription.
- Aberrant ion channel expression is common in cancer, highlighting their role in disease.
Purpose of the Study:
- To review the roles of auxiliary subunits in calcium (Ca2+), potassium (K+), sodium (Na+), and chloride (Cl-) channels.
- To explore the link between ion channel auxiliary subunits and cancer development.
- To identify potential biomarkers and therapeutic targets within ion channel auxiliary subunits.
Main Methods:
- Literature review focusing on conducting and non-conducting roles of auxiliary subunits.
- Analysis of studies linking auxiliary subunits to cancer, including gene expression changes and functional implications.
- Examination of in vivo studies implicating subunits as oncogenes or tumor suppressor genes.
Main Results:
- Several auxiliary subunits are differentially expressed in cancer (e.g., upregulated CaVβ, CaVγ; downregulated Kvβ).
- Specific subunits like Navβ1 and CaVα2δ1 are implicated as oncogenes.
- Other subunits, including CLCA2, KCNE2, and BKγ1, function as tumor suppressor genes.
Conclusions:
- Ion channel auxiliary subunits play significant roles in cancer progression.
- These subunits represent promising biomarkers and therapeutic targets for cancer treatment.
- Further research is needed to elucidate the precise mechanisms by which auxiliary subunits contribute to tumor progression.
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