Figure 7. Proposed working-model of PANX1-mediated ATP release as a regulator of intravascular metastatic cell survival.

Schematic showing stretch-induced ATP release through mechanosensitive PANX1 channels activating a cancer cell-autonomous purinergic signaling pathway that inhibits cell death during mechanical stress in the microvasculature of target organs. Those cancer cells enabled to secrete the levels of extracellular ATP necessary to permit intravascular survival via autocrine purinergic signaling pathways, or the adjacent cells lodged within the same tumor cell cluster, are afforded an opportunity to undergo the subsequent steps of the metastatic cascade—extravasation, colonization, re-initiation and proliferation.