Mechanisms underlying the opposing effects of P2Y receptors on the cell cycle.

The purinergic P2Y receptors are critical determinants of physiological function playing diverse roles in cell proliferation, differentiation, and survival. However, in cancer cells they have been reported to assume contradictory roles at times, thus causing inhibition of proliferation, cell death, and apoptosis. A critical evaluation and analysis of the existing experimental data show that this response is caused by multiple mechanisms at the level of the ligand, receptor, G protein, intracellular signaling, such as the mitogen activated protein kinase pathways and surface expression. This review addresses the impact of these factors in determining the outcome of P2Y receptor activation. Working in conjunction, these factors can act to produce the observed opposing effects on the cell cycle. Thus, they are important factors in the pathogenesis and control of cancer.