Roles of G-protein-coupled receptor signaling in cancer biology and gene transcription.

G-protein-coupled receptors (GPCRs) are ubiquitous mediators of signal transduction across mammalian cell membranes. Among other roles, GPCRs are known to regulate cellular motility, growth and differentiation, and gene transcription, three factors central to the biology of cancer. Because GPCRs are tractable drug targets, mechanisms by which receptors and their associated proteins impact cellular transformation and metastasis might lead to novel cancer therapies. Recent work has elucidated mechanisms explaining correlations between cancer progression and the expression of GPCRs, such as a protease-activated receptor (PAR1), and G-proteins, such as Galpha(12/13). Of special interest, the discovery of novel nuclear roles for heterotrimeric G-proteins expands the direct impact of G-protein signaling on processes fundamental to the pathology of cancer.