A model for the regulation of T-type Ca²⁺ channels in proliferation: roles in stem cells and cancer

Abstract

Ca²⁺ influx at critical points in the cell cycle is required for proliferation. This requirement is so ubiquitous that its occurrence is often treated as background noise. Yet without it, cells stop dividing, suggesting an obvious and potentially effective way to treat cancer. To control proliferation by controlling Ca²⁺ influx requires that the mechanism be elucidated, but this field of study has been filled with controversy and devoid of therapeutic utility. In this study, the authors present a model for the regulation of Ca²⁺ influx at the G1/S restriction point in cancer and stem cells that is simple, cohesive and, we believe, reasonably complete. The model illustrates the essential role of T-type Ca²⁺ channels in mediating influx and points clearly to the therapeutic strategies that have recently entered clinical trials.

Keywords::

• cancer
• Cav3.2
• cell cycle
• membrane potential
• potassium channel
• proliferation
• stem cell
• T-type calcium channel

Financial & competing interests disclosure

LS Gray and TL Macdonald are co-founders of and consultants to Tau Therapeutics, LLC and D Schiff is a consultant to Tau Therapeutics, LLC. Tau Therapeutics, LLC is a pharmaceutical company working in oncology. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.