Roles of LPA in ovarian cancer development and progression

Abstract

Lysophosphatidic acid (LPA), a bioactive phospholipid, stimulates survival, proliferation, adhesion, migration and invasion of ovarian cancer cells through the activation of G-protein-coupled plasma membrane receptors. LPA and its receptors are aberrantly expressed in ovarian cancer, with high levels predominantly found in malignant ascites and in the plasma of ovarian cancer patients. LPA signals multiple intracellular pathways, such as Ras/MEKK1-MAPK and PI3K/Akt, to promote growth factors and protease expression, and induce angiogenesis and tumor cell invasion through the extracellular matrix and across the basement membrane. Only a small portion of this intricate lipid-signaling cascade has been characterized thus far. We believe that elucidation of this complex transduction network will provide further opportunities to understand the mechanism of ovarian carcinogenesis, invasion and metastasis.