Regulation of Cell Proliferation and Migration by Extracellular Phosphatidic Acid

Phosphatidic acid (PA) is increasingly recognized as an important endogenous regulator of cell proliferation and migration, playing relevant roles in physiology and pathology. However, the potential and prominence of extracellular PA in controlling cell functions are not so well established. The present review article has been undertaken to update and discuss the latest findings on extracellular PA as regulator of cell homeostasis, with special attention being paid to its role in the regulation of cell growth and migration. Specifically, exogenous PA potently stimulates myoblast proliferation, and lung cancer cell migration, pointing to a critical role of this glycerophospholipid in the regulation of muscle cell regeneration and lung cancer dissemination. Interestingly, both of these actions are mediated through interaction of PA with lysophosphatidic acid (LPA) receptors and the subsequent activation of different signal transduction pathways. In particular, PA induces mitogen-activated protein kinase kinase (MEK)/extracellularly regulated kinases (ERK) 1 and 2, phosphatidylinositol 3-kinase (PI3K)/Akt, focal adhesion kinase (FAK)/Rac1, and Janus kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3). These findings may contribute to a better understanding of muscle cell biology, and may help to develop new therapeutic strategies to treat lung cancer dissemination.