KiSS1-Induced GPR54 Signaling Inhibits Breast Cancer Cell Migration and Epithelial-Mesenchymal Transition via Protein Kinase D1

ISSN: 1875-5666 (Online)
ISSN: 1566-5240 (Print)


Volume 14, 10 Issues, 2014


Download PDF Flyer




Current Molecular Medicine

Aims & ScopeAbstracted/Indexed in

Ranking and Category:
  • 31st of 122 in Medicine, Research & Experimental

Submit Abstracts Online Submit Manuscripts Online

Editor-in-Chief:
David W. Li
College of Medicine
University of Nebraska Medical Center
Omaha, NE
USA


View Full Editorial Board

Subscribe Purchase Articles Order Reprints

Current: 3.612
5 - Year: 4.159

KiSS1-Induced GPR54 Signaling Inhibits Breast Cancer Cell Migration and Epithelial-Mesenchymal Transition via Protein Kinase D1

Author(s): K. Tan, S.-G. Cho, W. Luo, T. Yi, X. Wu, S. Siwko, M. Liu and W. Yuan

Affiliation: College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, P.R. China.

Abstract

The metastasis suppressor protein Kisspeptin regulates cancer cell proliferation and motility through its receptor, GRP54. However, the critical downstream effectors remain unclear. In this study, we investigated GPR54 signaling in breast cancer cells. Kisspeptin stimulation caused a decrease in migration of multiple breast cancer cell lines. Also, Kisspeptin inhibited MDA-MB-231 cell colony formation in 3D matrigel culture and in soft agar. Kisspeptin treatment elevated phosphorylated PKD1 in a PKC-dependent manner. However, knockdown of either GPR54 or PKD1 increased breast cancer cell migration and invasion. Furthermore, GPR54 knockdown blocked Kisspeptin-induced phosphorylation of PKD1. Finally, Kisspeptin stimulation induced a PKD1 phosphorylation-dependent decrease in expression of Slug, a transcription factor that drives epithelial-mesenchymal transition (EMT), and a concomitant increase in E-cadherin expression. Therefore, KiSS1/GPR54 signaling through PKD1 acts to maintain the epithelial state and to inhibit breast cancer cell invasiveness, and exerts functions associated with its role as a metastasis suppressor.

Keywords: Breast cancer, G protein coupled receptors (GPCR), GPR54, invasion, KiSS1, migration, protein kinase D (PKD).

Purchase Online Rights and Permissions

  
  



Article Details

Volume: 14
Issue Number: 5
First Page: 652
Last Page: 662
Page Count: 11
DOI: 10.2174/1566524014666140603115314
Advertisement

Related Journals




Webmaster Contact: urooj@benthamscience.org Copyright © 2014 Bentham Science