Membrane voltage and connexin expression work together to enhance tumor growth and metastasis in cancer

Tumors exhibit a unique membrane voltage, often depolarized at around -30mV, as opposed to normal cells with a resting potential of approximately -70mV. This depolarization is thought to expedite cell cycle progression and support tumor proliferation. However, as tumors become invasive, some of their cells undergo a shift to a hyperpolarized membrane voltage, a behavior not easily explained.

It is also known that invasive tumors express less connexin protein compared to healthy tissue, while non-invasive tumors display reduced connexin expression. The paradoxical behavior of connexin expression in relation to membrane voltage remains unexplained.

The electrical properties of these tumors, specifically the membrane voltage, have a direct impact on the formation and function of gap junctions, which are small channels that connect neighboring cells. When homotypic gap junctions (those connecting cells of the same cell type) are formed, their conductivity is optimized when the two cells share a similar membrane voltage.

By integrating findings from computational modeling, it has been demonstrated that tumor cells strategically manipulate both their membrane voltage and connexin expression to effectively control communication between themselves and their neighboring healthy cells. This insight into the interplay between electrochemical properties and connexin expression in tumors could pave the way for more targeted and precise cancer therapies within the emerging field of cancer bioelectrics.