Membrane potential and cancer progression

Abstract

Membrane potential (Vm), the voltage across the plasma membrane, arises because of the presence of different ion channels/transporters with specific ion selectivity and permeability. Vm is a key biophysical signal in non-excitable cells, modulating important cellular activities, such as proliferation and differentiation. Therefore, the multiplicities of various ion channels/transporters expressed on different cells are finely tuned in order to regulate the Vm. It is well-established that cancer cells possess distinct bioelectrical properties. Notably, electrophysiological analyses in many cancer cell types have revealed a depolarized Vm that favors cell proliferation. Ion channels/transporters control cell volume and migration, and emerging data also suggest that the level of Vm has functional roles in cancer cell migration. In addition, hyperpolarization is necessary for stem cell differentiation. For example, both osteogenesis and adipogenesis are hindered in human mesenchymal stem cells (hMSCs) under depolarizing conditions. Therefore, in the context of cancer, membrane depolarization might be important for the emergence and maintenance of cancer stem cells (CSCs), giving rise to sustained tumor growth. This review aims to provide a broad understanding of the Vm as a bioelectrical signal in cancer cells by examining several key types of ion channels that contribute to its regulation. The mechanisms by which Vm regulates cancer cell proliferation, migration, and differentiation will be discussed. In the long term, Vm might be a valuable clinical marker for tumor detection with prognostic value, and could even be artificially modified in order to inhibit tumor growth and metastasis.

Voltage-Dependent Calcium Channels in Chondrocytes: Roles in Health and Disease

“…As discussed earlier, even though the chondrocyte is a nonexcitable cell type, RMP acts as a key biophysical signal modulating important activities such as volume regulation, proliferation, and differentiation [30]. To identify what roles VDCCs may play in the regulation of chondrocyte proliferation and RMP, several studies have been conducted.…”

Effect of low voltage AC fields on cardiovascular implants

“…Several theories correlating cancerous cells to depolarised voltage membrane potential (Vmem) values have been discussed in the literature [17,18]. Typical membrane potential values for healthy tissue range between -10mV to -90mV as shown in figure 5 [17,18,19].…”

“…Several theories correlating cancerous cells to depolarised voltage membrane potential (Vmem) values have been discussed in the literature [17,18]. Typical membrane potential values for healthy tissue range between -10mV to -90mV as shown in figure 5 [17,18,19]. It can be seen that tumour cells and certain non-tumour cells such as proliferating fibroblasts and 3T3 cells possess lower membrane potential values; hence further research has suggested that ion channels/transporters such as Na+, Ca2+, K+, and Cl-(Sodium Ion, Calcium Ion, Potassium ion and Chlorine ion respectively) are contributing 10 factors to cancer progression.…”

Targeting potassium channels in cancer

“…Compared with the more hyperpolarized resting membrane potential in differentiated cell types such as neurons or cardiomyocytes (60 to 80 mV), rapidly proliferating embryonic cells, stem cells, or cancer cell are in general more depolarized, with a resting membrane potential at 20 to 40 mV (Yang and Brackenbury, 2013). Therefore, one classical hypothesis is that membrane depolarization itself plays a functional role in tumor initiation or progression (Fig.…”