LPA Receptors

Lysophosphatidic acid (LPA) is an extracellular lipid mediator that evokes growth factor-like responses, inducing cell proliferation, migration and survival, indicating a role in the initiation or progression of malignant disease.18 Increased levels of LPA have been detected in malignant effusions. Its receptors, particularly LPA2 and LPA3, are aberrantly expressed in several human cancers, particularly in ovarian and prostate cancer cells.19

In addition, autotaxin, an ectoenzyme known to be involved in tumor invasion, neovascularization, and metastasis, appears to act by producing LPA, further demonstrating a key role for LPA in the metastatic cascade.20

LPA signals not only via the classic second messengers but also activates RAS and Rho family GTPases — important switches that control cell proliferation, migration, and morphogenesis. In addition, LPA induces transactivation of the epidermal growth factor receptor (EGFR) through activation of metalloproteinases, thereby modulating the migratory and invasive behaviors of kidney and bladder cancer cells.21

Other potent mitogenic GPCR agonists such as thrombin, bombesin, bradykinin, and angiotensin II induce signals that converge on the EGFR to promote migration and invasion, suggesting a common signaling mechanism important in tumorigenesis.

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