Logo image
Back
PKCε Is an Essential Mediator of Prostate Cancer Bone Metastasis
Journal article   Open access   Peer reviewed

PKCε Is an Essential Mediator of Prostate Cancer Bone Metastasis

Alvaro Gutierrez-Uzquiza, Cynthia Lopez-Haber, Danielle L Jernigan, Alessandro Fatatis and Marcelo G Kazanietz
Molecular cancer research, v 13(9), pp 1336-1346
Sep 2015
DOI: https://doi.org/10.1158/1541-7786.MCR-15-0111
PMID: 26023164
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1158/1541-7786.mcr-15-0111View
Accepted (AM)Open Access (License Unspecified),  Open
url
https://doi.org/10.1158/1541-7786.MCR-15-0111View
Published, Version of Record (VoR) Open

Abstract

Animals Bone Neoplasms - secondary Cell Adhesion Cell Line, Tumor Cell Movement Cell Proliferation Heterografts Humans Interleukin-1beta - metabolism Male Mediator Complex Mice Mice, Nude Prostatic Neoplasms - metabolism Prostatic Neoplasms - pathology Protein Kinase C-epsilon - metabolism RNA, Small Interfering - metabolism
The bone is a preferred site for metastatic homing of prostate cancer cells. Once prostate cancer patients develop skeletal metastases, they eventually succumb to the disease; therefore, it is imperative to identify key molecular drivers of this process. This study examines the involvement of protein kinase C epsilon (PKCε), an oncogenic protein that is abnormally overexpressed in human tumor specimens and cell lines, on prostate cancer cell bone metastasis. PC3-ML cells, a highly invasive prostate cancer PC3 derivative with bone metastatic colonization properties, failed to induce skeletal metastatic foci upon inoculation into nude mice when PKCε expression was silenced using shRNA. Interestingly, while PKCε depletion had only marginal effects on the proliferative, adhesive, and migratory capacities of PC3-ML cells in vitro or in the growth of xenografts upon s.c. inoculation, it caused a significant reduction in cell invasiveness. Notably, PKCε was required for transendothelial cell migration (TEM) as well as for the growth of PC3-ML cells in a bone biomimetic environment. At a mechanistic level, PKCε depletion abrogates the expression of IL1β, a cytokine implicated in skeletal metastasis. Taken together, PKCε is a key factor for driving the formation of bone metastasis by prostate cancer cells and is a potential therapeutic target for advanced stages of the disease. This study uncovers an important new function of PKCε in the dissemination of cancer cells to the bone; thus, highlighting the promising potential of this oncogenic kinase as a therapeutic target for skeletal metastasis.

Metrics

16 Record Views
33 citations in Web of Science
34 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
Web of Science research areas
Cell Biology
Oncology
Logo image