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Steroid Receptor Coactivator-2 Controls the Pentose Phosphate Pathway through RPIA in Human Endometrial Cancer Cells.

Sci Rep. 2018 Sep 03;8(1):13134
Maria M Szwarc 1 , Ramakrishna Kommagani 2 , Vasanta Putluri 3 , Julien Dubrulle 3 , Fabio Stossi 3 , Michael A Mancini 3 , Cristian Coarfa 1 , Rainer B Lanz 1 , Nagireddy Putluri 3 , Francesco J DeMayo 4 , John P Lydon 5 , Bert W O'Malley 6
Maria M Szwarc 1 , Ramakrishna Kommagani 2 , Vasanta Putluri 3 , Julien Dubrulle 3 , Fabio Stossi 3 , Michael A Mancini 3 , Cristian Coarfa 1 , Rainer B Lanz 1 , Nagireddy Putluri 3 , Francesco J DeMayo 4 , John P Lydon 5 , Bert W O'Malley 6
+ et al

[No authors listed]

Author information
  • 1 Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
  • 2 Department of Obstetrics & Gynecology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • 3 Advanced Technology Cores, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
  • 4 Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
  • 5 Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas, USA. jlydon@bcm.edu.
  • 6 Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas, USA. berto@bcm.edu.

摘要


Steroid receptor coactivator-2 (SRC-2) is a transcriptional coregulator that modulates the activity of many transcription factors. Levels of SRC-2 are elevated in endometrial biopsies from polycystic ovary syndrome patients, a population predisposed to endometrial cancer (EC). Increased expression of SRC-2 is also detected in neoplastic endometrium suggesting a causal link between elevated SRC-2 expression and the emergence of endometrial disorders that can lead to cancer. Here, we reveal that SRC-2 knockdown reduces EC cell proliferation and anchorage-independence. Additionally, SRC-2 is required to maintain cellular glycolytic capacity and oxidative phosphorylation, processes essential for EC cell proliferation. Importantly, SRC-2 is critical for the normal performance of the pentose phosphate pathway (PPP). Perturbation of the PPP due to loss of SRC-2 expression may result from the depletion of ribose-5-P isomerase (RPIA), a key enzyme of the PPP. As with SRC-2, RPIA knockdown reduces EC cell proliferation, which is accompanied by a decrease in glycolytic capacity and oxidative phosphorylation. Glucose metabolite tracking experiments confirmed that knockdown of SRC-2 and RPIA downregulates the metabolic rate of both glycolysis and the PPP, highlighting a novel regulatory cross-talk between glycolysis and the PPP modulated by SRC-2.