Hexokinase 2-Mediated Warburg Effect Is Required for PTEN- and p53-Deficiency-Driven Prostate Cancer Growth

Lei Wang, Hua Xiong, Fengxia Wu, Yingjie Zhang, Ji Wang, Liyan Zhao, Xiaolan Guo, Li Ju Chang, Yong Zhang, M. James You, Shahriar Koochekpour, Mohammad Saleem, Haojie Huang, Junxuan Lu, Yibin Deng

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Accumulating evidence suggests that codeletion ofthe tumor suppressor genes Pten and p53 plays a crucial role in the development of castration-resistant prostate cancer invivo. However, the molecular mechanism underlying Pten- /p53-deficiency-driven prostate tumorigenesis remains incompletely understood. Building upon insights gained from our studies with Pten-/. p53-deficient mouse embryonic fibroblasts (MEFs), we report here that hexokinase 2 (HK2) is selectively upregulated by the combined loss of Pten and p53 in prostate cancer cells. Mechanistically, Pten deletion increases HK2 mRNA translation through the activation of the AKT-mTORC1-4EBP1 axis, and p53 loss enhances HK2 mRNA stability through the inhibition of miR143 biogenesis.Genetic studies demonstrate that HK2-mediated aerobic glycolysis, known as the Warburg effect, is required for Pten-/. p53-deficiency-driven tumor growth in xenograft mouse models of prostate cancer. Our findings suggest that HK2 might be a therapeutic target for prostate cancer patients carrying Pten and p53 mutations.

Original languageEnglish (US)
Pages (from-to)1461-1474
Number of pages14
JournalCell Reports
Volume8
Issue number5
DOIs
StatePublished - Jan 1 2014

Fingerprint

Hexokinase
Prostatic Neoplasms
Growth
Tumors
Messenger RNA
Castration
RNA Stability
Protein Biosynthesis
Glycolysis
Fibroblasts
Tumor Suppressor Genes
Heterografts
Prostate
Carcinogenesis
Genes
Chemical activation
Cells
Mutation
Neoplasms

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Wang, Lei ; Xiong, Hua ; Wu, Fengxia ; Zhang, Yingjie ; Wang, Ji ; Zhao, Liyan ; Guo, Xiaolan ; Chang, Li Ju ; Zhang, Yong ; You, M. James ; Koochekpour, Shahriar ; Saleem, Mohammad ; Huang, Haojie ; Lu, Junxuan ; Deng, Yibin. / Hexokinase 2-Mediated Warburg Effect Is Required for PTEN- and p53-Deficiency-Driven Prostate Cancer Growth. In: Cell Reports. 2014 ; Vol. 8, No. 5. pp. 1461-1474.
@article{1fdc139eec734e9abad0e4ef414596f5,
title = "Hexokinase 2-Mediated Warburg Effect Is Required for PTEN- and p53-Deficiency-Driven Prostate Cancer Growth",
abstract = "Accumulating evidence suggests that codeletion ofthe tumor suppressor genes Pten and p53 plays a crucial role in the development of castration-resistant prostate cancer invivo. However, the molecular mechanism underlying Pten- /p53-deficiency-driven prostate tumorigenesis remains incompletely understood. Building upon insights gained from our studies with Pten-/. p53-deficient mouse embryonic fibroblasts (MEFs), we report here that hexokinase 2 (HK2) is selectively upregulated by the combined loss of Pten and p53 in prostate cancer cells. Mechanistically, Pten deletion increases HK2 mRNA translation through the activation of the AKT-mTORC1-4EBP1 axis, and p53 loss enhances HK2 mRNA stability through the inhibition of miR143 biogenesis.Genetic studies demonstrate that HK2-mediated aerobic glycolysis, known as the Warburg effect, is required for Pten-/. p53-deficiency-driven tumor growth in xenograft mouse models of prostate cancer. Our findings suggest that HK2 might be a therapeutic target for prostate cancer patients carrying Pten and p53 mutations.",
author = "Lei Wang and Hua Xiong and Fengxia Wu and Yingjie Zhang and Ji Wang and Liyan Zhao and Xiaolan Guo and Chang, {Li Ju} and Yong Zhang and You, {M. James} and Shahriar Koochekpour and Mohammad Saleem and Haojie Huang and Junxuan Lu and Yibin Deng",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.celrep.2014.07.053",
language = "English (US)",
volume = "8",
pages = "1461--1474",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "5",

}

Wang, L, Xiong, H, Wu, F, Zhang, Y, Wang, J, Zhao, L, Guo, X, Chang, LJ, Zhang, Y, You, MJ, Koochekpour, S, Saleem, M, Huang, H, Lu, J & Deng, Y 2014, 'Hexokinase 2-Mediated Warburg Effect Is Required for PTEN- and p53-Deficiency-Driven Prostate Cancer Growth', Cell Reports, vol. 8, no. 5, pp. 1461-1474. https://doi.org/10.1016/j.celrep.2014.07.053

Hexokinase 2-Mediated Warburg Effect Is Required for PTEN- and p53-Deficiency-Driven Prostate Cancer Growth. / Wang, Lei; Xiong, Hua; Wu, Fengxia; Zhang, Yingjie; Wang, Ji; Zhao, Liyan; Guo, Xiaolan; Chang, Li Ju; Zhang, Yong; You, M. James; Koochekpour, Shahriar; Saleem, Mohammad; Huang, Haojie; Lu, Junxuan; Deng, Yibin.

In: Cell Reports, Vol. 8, No. 5, 01.01.2014, p. 1461-1474.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Hexokinase 2-Mediated Warburg Effect Is Required for PTEN- and p53-Deficiency-Driven Prostate Cancer Growth

AU - Wang, Lei

AU - Xiong, Hua

AU - Wu, Fengxia

AU - Zhang, Yingjie

AU - Wang, Ji

AU - Zhao, Liyan

AU - Guo, Xiaolan

AU - Chang, Li Ju

AU - Zhang, Yong

AU - You, M. James

AU - Koochekpour, Shahriar

AU - Saleem, Mohammad

AU - Huang, Haojie

AU - Lu, Junxuan

AU - Deng, Yibin

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Accumulating evidence suggests that codeletion ofthe tumor suppressor genes Pten and p53 plays a crucial role in the development of castration-resistant prostate cancer invivo. However, the molecular mechanism underlying Pten- /p53-deficiency-driven prostate tumorigenesis remains incompletely understood. Building upon insights gained from our studies with Pten-/. p53-deficient mouse embryonic fibroblasts (MEFs), we report here that hexokinase 2 (HK2) is selectively upregulated by the combined loss of Pten and p53 in prostate cancer cells. Mechanistically, Pten deletion increases HK2 mRNA translation through the activation of the AKT-mTORC1-4EBP1 axis, and p53 loss enhances HK2 mRNA stability through the inhibition of miR143 biogenesis.Genetic studies demonstrate that HK2-mediated aerobic glycolysis, known as the Warburg effect, is required for Pten-/. p53-deficiency-driven tumor growth in xenograft mouse models of prostate cancer. Our findings suggest that HK2 might be a therapeutic target for prostate cancer patients carrying Pten and p53 mutations.

AB - Accumulating evidence suggests that codeletion ofthe tumor suppressor genes Pten and p53 plays a crucial role in the development of castration-resistant prostate cancer invivo. However, the molecular mechanism underlying Pten- /p53-deficiency-driven prostate tumorigenesis remains incompletely understood. Building upon insights gained from our studies with Pten-/. p53-deficient mouse embryonic fibroblasts (MEFs), we report here that hexokinase 2 (HK2) is selectively upregulated by the combined loss of Pten and p53 in prostate cancer cells. Mechanistically, Pten deletion increases HK2 mRNA translation through the activation of the AKT-mTORC1-4EBP1 axis, and p53 loss enhances HK2 mRNA stability through the inhibition of miR143 biogenesis.Genetic studies demonstrate that HK2-mediated aerobic glycolysis, known as the Warburg effect, is required for Pten-/. p53-deficiency-driven tumor growth in xenograft mouse models of prostate cancer. Our findings suggest that HK2 might be a therapeutic target for prostate cancer patients carrying Pten and p53 mutations.

UR - http://www.scopus.com/inward/record.url?scp=84922503253&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922503253&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2014.07.053

DO - 10.1016/j.celrep.2014.07.053

M3 - Article

C2 - 25176644

AN - SCOPUS:84922503253

VL - 8

SP - 1461

EP - 1474

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 5

ER -