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

Montal, E. D., Dewi, R., Bhalla, K., Ou, L., Hwang, B. J., Ropell, A. E., Gordon, C., Liu, W. J., DeBerardinis, R. J., Sudderth, J., Twaddel, W., Boros, L. G., Shroyer, K. R., Duraisamy, S., Drapkin, R., Powers, R. S., Rohde, J. M., Boxer, M. B., Wong, K. K., Girnun, G. D. (November 2015) PEPCK Coordinates the Regulation of Central Carbon Metabolism to Promote Cancer Cell Growth. Mol Cell, 60 (4). pp. 571-83. ISSN 1097-2765

URL: https://www.ncbi.nlm.nih.gov/pubmed/26481663
DOI: 10.1016/j.molcel.2015.09.025

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.

Item Type: Paper
Uncontrolled Keywords: Animals Cell Line, Tumor Cell Proliferation Colorectal Neoplasms/metabolism/*pathology Glucose/*metabolism Glutamine/*metabolism Glycolysis HT29 Cells Humans Mechanistic Target of Rapamycin Complex 1 Mice Multiprotein Complexes/*metabolism Neoplasm Transplantation Phosphoenolpyruvate Carboxykinase (ATP)/*metabolism TOR Serine-Threonine Kinases/*metabolism
Subjects: diseases & disorders > cancer
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell proliferation
CSHL Authors:
Communities: CSHL Cancer Center Program > Cancer Genetics
CSHL labs > Powers lab
Depositing User: Matt Covey
Date: 19 November 2015
Date Deposited: 06 Mar 2018 20:17
Last Modified: 06 Mar 2018 20:17
PMCID: PMC4656111
Related URLs:
URI: http://repository.cshl.edu/id/eprint/36178

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