Phosphatidic Acid Stimulates Lung Cancer Cell Migration through Interaction with the LPA1 Receptor and Subsequent Activation of MAP Kinases

Phosphatidic acid (PA) is a key bioactive glycerophospholipid that implicated in the regulation of vital cell functions such as growth, differentiation, and migration, involved variety pathologic processes. However, molecular mechanisms by which PA exerts its pathophysiological actions are incompletely understood. In present work, we demonstrate stimulates migration human non-small lung cancer (NSCLC) A549 adenocarcinoma cells, determined transwell assay. induced rapid phosphorylation mitogen-activated protein kinases (MAPKs) ERK1-2, p38, JNK, pretreatment cells with selective inhibitors these blocked PA-stimulated cells. addition, chemotactic effect was inhibited preincubating pertussis toxin (PTX), Gi inhibitor, suggesting implication protein-coupled receptor this action. Noteworthy, blockade LPA 1 (LPA1) specific LPA1 antagonist AM966, or Ki1645 VPC32193, abolished migration. Moreover, stimulated transcription factor STAT3 downstream JAK2, either JAK2 It can be concluded through an interaction subsequent activation MAPKs JAK2/STAT3 pathway also important process. These findings suggest targeting formation and/or may provide new strategies to reduce malignancy cancer.