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Data from SOX4 Is Essential for Prostate Tumorigenesis Initiated by PTEN Ablation
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Data from SOX4 Is Essential for Prostate Tumorigenesis Initiated by PTEN Ablation
Data from SOX4 Is Essential for Prostate Tumorigenesis Initiated by PTEN Ablation
BB
Birdal Bilir
Birdal Bilir
AO
Adeboye O. Osunkoya
Adeboye O. Osunkoya
WW
W. Guy Wiles
W. Guy Wiles
SS
Soma Sannigrahi
Soma Sannigrahi
VL
Veronique Lefebvre
Veronique Lefebvre
DM
Daniel Metzger
Daniel Metzger
DS
Demetri D. Spyropoulos
Demetri D. Spyropoulos
WM
W. David Martin
W. David Martin
CM
Carlos S. Moreno
Carlos S. Moreno
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30 March 2023
other
Published by
American Association for Cancer Research (AACR)
https://doi.org/10.1158/0008-5472.c.6507596.v1
Abstract
Understanding remains incomplete of the mechanisms underlying initiation and progression of prostate cancer, the most commonly diagnosed cancer in American men. The transcription factor SOX4 is overexpressed in many human cancers, including prostate cancer, suggesting it may participate in prostate tumorigenesis. In this study, we investigated this possibility by genetically deleting Sox4 in a mouse model of prostate cancer initiated by loss of the tumor suppressor Pten. We found that specific homozygous deletion of Sox4 in the adult prostate epithelium strongly inhibited tumor progression initiated by homozygous loss of Pten. Mechanistically, Sox4 ablation reduced activation of AKT and β-catenin, leading to an attenuated invasive phenotype. Furthermore, SOX4 expression was induced by Pten loss as a result of the activation of PI3K–AKT–mTOR signaling, suggesting a positive feedback loop between SOX4 and PI3K–AKT–mTOR activity. Collectively, our findings establish that SOX4 is a critical component of the PTEN/PI3K/AKT pathway in prostate cancer, with potential implications for combination-targeted therapies against both primary and advanced prostate cancers. Cancer Res; 76(5); 1112–21. ©2015 AACR.
Keywords
TRANSCRIPTION FACTOR
SOX4
PTEN
DELETING
HOMOZYGOUS
PI3K
MTOR
PROSTATE CANCER
ADULT
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Open Access