title: Progranulin stimulated by LPA promotes the migration of aggressive breast cancer cells.
abstract: Activator and inhibitor roles for the 88-kDa-secreted glycoprotein progranulin (PGRN) have been demonstrated in ovarian cancer cells. Here, we investigated the effects of PGRN in breast cancer migration. Testing MCF7, MDA-MB-453, and MDA-MB-231 human breast cancer cells and the MCF10A breast epithelial cell line, we demonstrate that LPA-induced PGRN stimulation led to a significant increase in cell invasion of MDA-MB-453 and MDA-MB-231 cells only (p<0.05). Moreover, incubation with an anti-PGRN antibody, an inhibitor of the ERK pathway (PD98059) or both in combination inhibited the ability of MDA-MB-231 cells to invade. Furthermore, the expression of focal adhesion kinases promoted by LPA-induced PGRN was also inhibited by PD98059 alone or in combination with an anti-PGRN antibody (p<0.05). Taken together, these results suggest that the LPA activation of PGRN involving the ERK pathway is critical to promote MDA-MB-231 breast cancer cell invasion.
authors.affiliation: Cellular and Molecular Division, Department of Biology, University of North Carolina-Charlotte, University City Blvd, Charlotte, NC 28223, USA.
authors.forename: Muthulekha
authors.initials: M
authors.lastname: Swamydas
authors.forename: Do
authors.initials: D
authors.lastname: Nguyen
authors.forename: Lauren D
authors.initials: LD
authors.lastname: Allen
authors.forename: Jill
authors.initials: J
authors.lastname: Eddy
authors.forename: Didier
authors.initials: D
authors.lastname: Dréau
mesh_terms: D000906:Antibodies / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008246:Lysophospholipids / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness / Q000473:pathology; D000077153:Progranulins; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D000906:Antibodies; D005419:Flavonoids; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008246:Lysophospholipids; D000077153:Progranulins; D034741:RNA, Small Interfering; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C032881:lysophosphatidic acid; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one