Volume 2 Supplement 1

Metabolism, Diet and Disease 2014: Cancer and metabolism

Open Access

Acetyl-coA synthetase 2 promotes acetate utilization and maintains cell growth under metabolic stress

  • Zachary Schug1,
  • Barrie Peck2,
  • Dylan Jones3,
  • Qifeng Zhang4,
  • Israt Alam5,
  • Tim Witney5,
  • Elizabeth Smethurst4,
  • Shaun Grosskurth6,
  • Adrian Harris3,
  • Susan Critchlow6,
  • Eric Aboagye5,
  • Michael Wakelam4,
  • Almut Schulze2, 7 and
  • Eyal Gottlieb1
Cancer & Metabolism20142(Suppl 1):O9

https://doi.org/10.1186/2049-3002-2-S1-O9

Published: 28 May 2014

During tumour formation and expansion, cancer cells encounter constantly changing environmental conditions in which nutrient and oxygen availability may be severely compromised. The metabolic transformation of cancer cells is characterised by distinct changes in metabolic activity that satisfy the exigencies of energy and biomass production imposed by continued cell proliferation. These metabolic adaptations often involve increased consumption and metabolism of extracellular nutrients, mainly glucose, amino acids and lipids. During periods of nutrient or oxygen deprivation, cancer cells can also modify their metabolism to adapt to these specific challenges. Here we report the results of a functional genomics study that revealed that the activity of acetyl-coA synthetase 2, an enzyme that converts acetate into acetyl-coA, contributes to cellular growth under oxygen and nutrient stressed conditions. ACSS2 was required to provide acetyl groups for lipid biosynthesis. Moreover, ACSS2 was essential for cancer cell growth and survival under physiologically relevant growth conditions and its depletion blocked tumour growth in vivo. In summary, our data demonstrate a previously unappreciated role for acetate as a nutritional source for the growth and survival of breast and prostate cancer cells under metabolic stress.

Authors’ Affiliations

(1)
CR-UK The Beatson Institute
(2)
CR-UK London Research Institute
(3)
Weatherall Institute for Molecular Medicine
(4)
The Babraham Institute
(5)
Imperial College
(6)
AstraZeneca
(7)
Theodor Boveri Institute

Copyright

© Schug et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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