title: Signaling regulation and role of filamin A cleavage in Ca2+-stimulated migration of androgen receptor-deficient prostate cancer cells.
abstract: Ca2+, a ubiquitous cellular signal, and filamin A, an actin-binding protein, play an important role in the regulation of cell adhesion, shape and motility. Using transwell filters to analyze cell migration, we found that extracellular Ca2+ (Cao2+) promotes the migration of androgen receptor (AR)-deficient and highly metastatic prostate cancer cell lines (DU145 and PC-3) compared to AR-positive and relatively less metastatic prostate cancer cells (LNCaP). Furthermore, we found that expression of filamin A is up-regulated in DU145 and PC-3 cells, and that Cao2+ significantly induces the cleavage of filamin A. Silencing expression of Ca2+-sensing receptor (CaR) and p115RhoGEF, and treating with leupeptin, a protease inhibitor, and ALLM, a calpain specific inhibitor, we further demonstrate that Cao2+-induced filamin A cleavage occurs via a CaR- p115RhoGEF-calpain dependent pathway. Our data show that Cao2+ via CaR- mediated signaling induces filamin A cleavage and promotes the migration in AR-deficient and highly metastatic prostate cancer cells.
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, Saint Louis University, Saint Louis, MO 63104, USA.
authors.forename: Chunfa
authors.initials: C
authors.lastname: Huang
authors.affiliation: Departments of Medicine and Dallas VAMC, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: R Tyler
authors.initials: RT
authors.lastname: Miller
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, Saint Louis University, Saint Louis, MO 63104, USA.
authors.forename: Carl E
authors.initials: CE
authors.lastname: Freter
mesh_terms: D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D064448:Filamins / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011944:Receptors, Androgen / Q000172:deficiency*; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: C410798:AR protein, human; C095550:CASR protein, human; C578663:FLNA protein, human; D064448:Filamins; D011944:Receptors, Androgen; D044169:Receptors, Calcium-Sensing; D002118:Calcium
keywords: AR-deficient prostate cancer cells; Ca2+-sensing receptor; calpain; filamin a cleavage; p115RhoGEF