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

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

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+ (Cao 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 Cao 2+ 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 Cao 2+-induced filamin A cleavage occurs via a CaR- p115RhoGEF-calpain dependent pathway. Our data show that Cao 2+ via CaR- mediated signaling induces filamin A cleavage and promotes the migration in AR-deficient and highly metastatic prostate cancer cells.

Original languageEnglish (US)
Pages (from-to)3840-3853
Number of pages14
JournalOncotarget
Volume8
Issue number3
DOIs
StatePublished - 2017

Fingerprint

Filamins
Androgen Receptors
Prostatic Neoplasms
Rho Guanine Nucleotide Exchange Factors
Calcium-Sensing Receptors
Cell Movement
Microfilament Proteins
Calpain
Cell Shape
Protease Inhibitors
Cell Adhesion
Cell Line

Keywords

  • AR-deficient prostate cancer cells
  • Ca-sensing receptor
  • Calpain
  • Filamin a cleavage
  • P115RhoGEF

ASJC Scopus subject areas

  • Oncology

Cite this

Signaling regulation and role of filamin A cleavage in Ca2+-stimulated migration of androgen receptor-deficient prostate cancer cells. / Huang, Chunfa; Miller, R. Tyler; Freter, Carl E.

In: Oncotarget, Vol. 8, No. 3, 2017, p. 3840-3853.

Research output: Contribution to journalArticle

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