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Steroid Receptor Coactivator-3 Regulates Glucose Metabolism in Bladder Cancer Cells through Coactivation of Hypoxia Inducible Factor 1α
The Journal of Biological Chemistry
  • Wei Zhao
  • Cunjie Chang
  • Yangyan Cui
  • Xiaozhi Zhao
  • Jun Yang
  • Lan Shen
  • Ji Zhou
  • Zhibo Hou
  • Zhen Zhang
  • Changxiao Ye
  • Donald Hasenmayer, Philadelphia College of Osteopathic Medicine
  • Robert Perkins, Philadelphia College of Osteopathic Medicine
  • Xiaojing Huang
  • Xin Yao
  • Like Yu
  • Ruimin Huang
  • Dianzheng Zhang, Philadelphia College of Osteopathic Medicine
  • Hongqian Guo
  • Jun Yan
Document Type
Article
Publication Date
4-18-2014
Abstract
Cancer cell proliferation is a metabolically demanding process, requiring high glycolysis, which is known as "Warburg effect," to support anabolic growth. Steroid receptor coactivator-3 (SRC-3), a steroid receptor coactivator, is overexpressed and/or amplified in multiple cancer types, including non-steroid targeted cancers, such as urinary bladder cancer (UBC). However, whether SRC-3 regulates the metabolic reprogramming for cancer cell growth is unknown. Here, we reported that overexpression of SRC-3 accelerated UBC cell growth, accompanied by the increased expression of genes involved in glycolysis. Knockdown of SRC-3 reduced the UBC cell glycolytic rate under hypoxia, decreased tumor growth in nude mice, with reduction of proliferating cell nuclear antigen and lactate dehydrogenase expression levels. We further revealed that SRC-3 could interact with hypoxia inducible factor 1α (HIF1α), which is a key transcription factor required for glycolysis, and coactivate its transcriptional activity. SRC-3 was recruited to the promoters of HIF1α-target genes, such as glut1 and pgk1. The positive correlation of expression levels between SRC-3 and Glut1 proteins was demonstrated in human UBC patient samples. Inhibition of glycolysis through targeting HK2 or LDHA decelerated SRC-3 overexpression-induced cell growth. In summary, overexpression of SRC-3 promoted glycolysis in bladder cancer cells through HIF1α to facilitate tumorigenesis, which may be an intriguing drug target for bladder cancer therapy.
PubMed ID
24584933
Comments

This article was published in Journal of Biological Chemistry, Volume 289, Number 16, April 18, 2014, Pages 11219-29.

The published version is available at http://dx.doi.org/10.1074/jbc.M113.535989

Copyright © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Citation Information
Wei Zhao, Cunjie Chang, Yangyan Cui, Xiaozhi Zhao, et al.. "Steroid Receptor Coactivator-3 Regulates Glucose Metabolism in Bladder Cancer Cells through Coactivation of Hypoxia Inducible Factor 1α" The Journal of Biological Chemistry Vol. 289 Iss. 16 (2014) p. 11219 - 11229
Available at: http://works.bepress.com/dianzheng_zhang/12/