Research Papers:

Signaling regulation and role of filamin A cleavage in Ca2+-stimulated migration of androgen receptor-deficient prostate cancer cells

Chunfa Huang, R. Tyler Miller and Carl E. Freter _

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Oncotarget. 2017; 8:3840-3853. https://doi.org/10.18632/oncotarget.9472

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Chunfa Huang1, R. Tyler Miller2, Carl E. Freter1

1Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, Saint Louis University, Saint Louis, MO 63104, USA

2Departments of Medicine and Dallas VAMC, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA

Correspondence to:

Chunfa Huang, email: [email protected]

Keywords: Ca2+-sensing receptor, filamin a cleavage, calpain, p115RhoGEF, AR-deficient prostate cancer cells

Received: March 04, 2015     Accepted: April 24, 2016     Published: May 19, 2016


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.

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