PEPCK Coordinates the Regulation of Central Carbon Metabolism to Promote Cancer Cell Growth

Emily D. Montal, Ruby Dewi, Kavita Bhalla, Lihui Ou, Bor Jang Hwang, Ashley E. Ropell, Chris Gordon, Wan Ju Liu, Ralph J. DeBerardinis, Jessica Sudderth, William Twaddel, Laszlo G. Boros, Kenneth R. Shroyer, Sekhar Duraisamy, Ronny Drapkin, R. Scott Powers, Jason M. Rohde, Matthew B. Boxer, Kwok Kin Wong, Geoffrey D. Girnun

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

Phosphoenolpyruvate carboxykinase (PEPCK) is well known for its role in gluconeogenesis. However, PEPCK is also a key regulator of TCA cycle flux. The TCA cycle integrates glucose, amino acid, and lipid metabolism depending on cellular needs. In addition, biosynthetic pathways crucial to tumor growth require the TCA cycle for the processing of glucose and glutamine derived carbons. We show here an unexpected role for PEPCK in promoting cancer cell proliferation in vitro and in vivo by increasing glucose and glutamine utilization toward anabolic metabolism. Unexpectedly, PEPCK also increased the synthesis of ribose from non-carbohydrate sources, such as glutamine, a phenomenon not previously described. Finally, we show that the effects of PEPCK on glucose metabolism and cell proliferation are in part mediated via activation of mTORC1. Taken together, these data demonstrate a role for PEPCK that links metabolic flux and anabolic pathways to cancer cell proliferation.

Original languageEnglish (US)
Pages (from-to)571-583
Number of pages13
JournalMolecular cell
Volume60
Issue number4
DOIs
StatePublished - Nov 19 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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