Lysophosphatidylethanolamine utilizes LPA(1) and CD97 in MDA-MB-231 breast cancer cells

作者：Park Soo Jin; Lee Kyoung Pil; Kang Saeromi; Chung Hae Young; Bae Yoe Sik; Okajima Fumikazu; Im Dong Soon^*

来源：Cellular Signalling, 2013, 25(11): 2147-2154.

DOI：10.1016/j.cellsig.2013.07.001

• Lysophosphatidylethanolamine
• LPA(1)
• Lysophosphatidic acid
• GPCR
• Breast
• Receptor

Lysophosphatidylethanolamine (LPE) is a lyso-type metabolite of phosphatidylethanolamine (a plasma membrane component), and its intracellular Ca2+ ([Ca2+](i)) increasing actions may be mediated through G-protein-coupled receptor (GPCR). However, GPCRs for lysophosphatidic acid (LPA), a structurally similar representative lipid mediator, have not been implicated in LPE-mediated activities in SK-0V3 or OVCAR-3 ovarian cancer cells or in receptor over-expression systems. In the present study, LPE-induced [Ca2+](i) increase was observed in MDA-MB-231 cells but not in other breast cancer cell lines. In addition, LPE- and LPA-induced responses showed homologous and heterologous desensitization. Furthermore, VPC32183 and Ki16425 (antagonists of LPA(1) and LPA(3)) inhibited LPE-induced [Ca2+](i) increases, and knockdown of LPA(1) by transfection with LPA(1) siRNA completely inhibited LPE-induced [Ca2+](i) increases. Furthermore, the involvement of CD97 (an adhesion GPCR) in the action of LPA(1) in MDA-MB-231 cells was demonstrated by siRNA transfection. Pertussis toxin (a specific inhibitor of G(i/o), proteins), edelfosine (an inhibitor of phospholipase C), or 2-APB (an inhibitor of IP3 receptor) completely inhibited LPE-induced [Ca2+](i) increases, whereas HA130, an inhibitor of autotaxin/lysophospholipase D, did not. Therefore, LPE is supposed to act on LPA(1)-CD97/G(i/o) proteins/phospholipase C/IP3/Ca2+ rise in MDA-MB-231 breast cancer cells.

• 出版日期2013-11