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Current Molecular Medicine
ISSN (Print): 1566-5240
ISSN (Online): 1875-5666
VOLUME: 14
ISSUE: 5
DOI: 10.2174/1566524014666140603115314      Price:  $58









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

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Author(s): K. Tan, S.-G. Cho, W. Luo, T. Yi, X. Wu, S. Siwko, M. Liu and W. Yuan
Pages 652-662 (11)
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).
Affiliation:
College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, P.R. China.