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

Maria M. Szwarc, Ramakrishna Kommagani, Vasanta Putluri, Julien Dubrulle, Fabio Stossi, Michael A. Mancini, Cristian Coarfa, Rainer B. Lanz, Nagireddy Putluri, Francesco J. DeMayo, John P. Lydon, Bert W. O’Malley

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

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.

Original languageEnglish
Article number13134
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint Dive into the research topics of 'Steroid Receptor Coactivator-2 Controls the Pentose Phosphate Pathway through RPIA in Human Endometrial Cancer Cells'. Together they form a unique fingerprint.

  • Cite this

    Szwarc, M. M., Kommagani, R., Putluri, V., Dubrulle, J., Stossi, F., Mancini, M. A., Coarfa, C., Lanz, R. B., Putluri, N., DeMayo, F. J., Lydon, J. P., & O’Malley, B. W. (2018). Steroid Receptor Coactivator-2 Controls the Pentose Phosphate Pathway through RPIA in Human Endometrial Cancer Cells. Scientific reports, 8(1), [13134]. https://doi.org/10.1038/s41598-018-31372-y