Pannexin biology and emerging linkages to cancer

Pannexins are a family of glycoproteins that comprises three members, PANX1, PANX2, and PANX3. The widely expressed and interrogated PANX1 forms heptameric membrane channels that primarily serve to connect the cytoplasm to the extracellular milieu by being selectively permeable to small signaling molecules when activated. Apart from notable exceptions, PANX1 in many tumor cells appears to facilitate tumor growth and metastasis, suggesting that pannexin-blocking therapeutics may have utility in cancer. Attenuation of PANX1 function must also consider the fact that PANX1 is found in stromal cells of the tumor microenvironment (TME), including immune cells. This review highlights the key discoveries of the past 5 years that suggest pannexins facilitate, or in some cases inhibit, tumor cell growth and metastasis via direct protein interactions and through the regulated efflux of signaling molecules.