Tristetraprolin disables prostate cancer maintenance by impairing proliferation and metabolic function

Tristetraprolin (TTP) is an RNA-binding protein that post-transcriptionally suppresses gene expression by delivering mRNA cargo to processing bodies (P-bodies) where the mRNA is degraded. TTP functions as a tumor suppressor in a mouse model of B cell lymphoma, and in some human malignancies low TTP...

Full description

Saved in:
Bibliographic Details
Published in:Oncotarget 2016-12, Vol.7 (50), p.83462-83475
Main Authors: Berglund, Anders E, Scott, Kristen E N, Li, Weimin, Yang, Chunying, Fernandez, Mario R, Schaub, Franz X, Cleveland, John L, Rounbehler, Robert J
Format: Article
Language:English
Subjects:
Animals
Antibiotics, Antineoplastic - pharmacology
Cell Line, Tumor
Cell Proliferation - drug effects
Disease-Free Survival
Dose-Response Relationship, Drug
Doxorubicin - pharmacology
Energy Metabolism - drug effects
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Humans
Kallikreins - blood
Male
Mice, Nude
Neoplasm Grading
Prostate-Specific Antigen - blood
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - genetics
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Research Paper
Signal Transduction
Time Factors
Tristetraprolin - genetics
Tristetraprolin - metabolism
Tumor Suppressor Proteins - genetics
Tumor Suppressor Proteins - metabolism
Xenograft Model Antitumor Assays
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Tristetraprolin (TTP) is an RNA-binding protein that post-transcriptionally suppresses gene expression by delivering mRNA cargo to processing bodies (P-bodies) where the mRNA is degraded. TTP functions as a tumor suppressor in a mouse model of B cell lymphoma, and in some human malignancies low TTP expression correlates with reduced survival. Here we report important prognostic and functional roles for TTP in human prostate cancer. First, gene expression analysis of prostate tumors revealed low TTP expression correlates with patients having high-risk Gleason scores and increased biochemical recurrence. Second, in prostate cancer cells with low levels of endogenous TTP, inducible TTP expression inhibits their growth and proliferation, as well as their clonogenic growth. Third, TTP functions as a tumor suppressor in prostate cancer, as forced TTP expression markedly impairs the tumorigenic potential of prostate cancer cells in a mouse xenograft model. Finally, pathway analysis of gene expression data suggested metabolism is altered by TTP expression in prostate tumor cells, and metabolic analyses revealed that such processes are impaired by TTP, including mitochondrial respiration. Collectively, these findings suggest that TTP is an important prognostic indicator for prostate cancer, and augmenting TTP function would effectively disable the metabolism and proliferation of aggressive prostate tumors.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.13128