Abstract
Cancer cells adapt metabolically to proliferate under nutrient limitation. Here we used combined transcriptional-metabolomic network analysis to identify metabolic pathways that support glucose-independent tumor cell proliferation. We found that glucose deprivation stimulated re-wiring of the tricarboxylic acid (TCA) cycle and early steps of gluconeogenesis to promote glucose-independent cell proliferation. Glucose limitation promoted the production of phosphoenolpyruvate (PEP) from glutamine via the activity of mitochondrial PEP-carboxykinase (PCK2). Under these conditions, glutamine-derived PEP was used to fuel biosynthetic pathways normally sustained by glucose, including serine and purine biosynthesis. PCK2 expression was required to maintain tumor cell proliferation under limited-glucose conditions in vitro and tumor growth in vivo. Elevated PCK2 expression is observed in several human tumor types and enriched in tumor tissue from non-small-cell lung cancer (NSCLC) patients. Our results define a role for PCK2 in cancer cell metabolic reprogramming that promotes glucose-independent cell growth and metabolic stress resistance in human tumors.
Original language | English |
---|---|
Pages (from-to) | 195-207 |
Number of pages | 13 |
Journal | Molecular Cell |
Volume | 60 |
Issue number | 2 |
DOIs | |
Publication status | Published - 15 Oct 2015 |
Bibliographical note
Date of Acceptance: 17/10/2015Fingerprint
Dive into the research topics of 'Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Metabolic Adaptation and Enables Glucose-Independent Tumor Growth'. Together they form a unique fingerprint.Profiles
-
Professor Jeremy M Tavare
- Life Sciences Faculty Office - Dean of Faculty of Life Sciences
- Fundamental Bioscience
- Cancer
- Dynamic Cell Biology
Person: Academic , Member
-
Dr Emma E Vincent
- Bristol Medical School (THS) - Senior Lecturer in Molecular Metabolism
- School of Cellular and Molecular Medicine - Research Fellow
- Bristol Population Health Science Institute
- Cancer
Person: Academic , Academic , Member