Signaling regulation and role of filamin A cleavage in Ca2+-stimulated migration of androgen receptor-deficient prostate cancer cells
Year: 2016
Type: article
Abstract: // Chunfa Huang 1 , R. Tyler Miller 2 , Carl E. Freter 1 1 Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, Saint Louis University, Saint Louis, MO 63104, USA 2 Departments of Medicine and Dallas VAMC, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA Correspondence to: Chunfa Huang, email: [email protected] Keywords: Ca 2+ -sensing receptor, filamin a cleavage, calpain, p115RhoGEF, AR-deficient prostate cancer cells Received: March 04, 2015 Accepted: April 24, 2016 Published: May 19, 2016 ABSTRACT Ca 2+ , 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 Ca 2+ (Ca o 2+ ) 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 Ca o 2+ significantly induces the cleavage of filamin A. Silencing expression of Ca 2+ -sensing receptor (CaR) and p115RhoGEF, and treating with leupeptin, a protease inhibitor, and ALLM, a calpain specific inhibitor, we further demonstrate that Ca o 2+ -induced filamin A cleavage occurs via a CaR- p115RhoGEF-calpain dependent pathway. Our data show that Ca o 2+ via CaR- mediated signaling induces filamin A cleavage and promotes the migration in AR-deficient and highly metastatic prostate cancer cells.
Source: Oncotarget
Authors: Chunfa Huang, R. Tyler Miller, Carl E. Freter
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W2401385367