Computational model proposes why tumours change membrane voltage and connexin levels as they become invasive

What happened

Two observations about tumours have lacked a joint explanation. Tumour cells are generally depolarised, with a resting membrane potential near -30 mV against roughly -70 mV for most fully differentiated cells, yet invasive tumour cells sometimes revert to a hyperpolarised state. Separately, solid tumours that are not yet invasive greatly underexpress connexins, the proteins that form gap junctions, while invasive tumours overexpress them.

The authors build on the fact that membrane voltage gates gap junctions: homotypic gap junctions conduct best when the two cells they connect have similar voltages. Their computational model shows that, taken together, a tumour's electrical state and its connexin expression form a single strategy for controlling communication between the tumour and its healthy neighbours.

Why it matters

If voltage and connexin levels are two parts of one mechanism, treatments aimed at either might be designed with the other in mind. The authors suggest the result could lead to more precisely targeted therapies in cancer bioelectrics.

Caveats

This is a preprint and has not been peer reviewed. The result comes from a computational model, with no experiments reported in the abstract, so it is a hypothesis about tumour behaviour, not evidence of it. This entry is based on the abstract. The preprint's record lists Astonishing Labs as a funder.