@article{PeckSchugZhangetal.2016,
  author    = {Peck, Barrie and Schug, Zachary T. and Zhang, Qifeng and Dankworth, Beatrice and Jones, Dylan T. and Smethurst, Elizabeth and Patel, Rachana and Mason, Susan and Jian, Ming and Saunders, Rebecca and Howell, Michael and Mitter, Richard and Spencer-Dene, Bradley and Stamp, Gordon and McGarry, Lynn and James, Daniel and Shanks, Emma and Aboagye, Eric O. and Critchlow, Susan E. and Leung, Hing Y. and Harris, Adrian L. and Wakelam, Michael J. O. and Gottlieb, Eyal and Schulze, Almut},
  title     = {Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments},
  series = {Cancer \& Metabolism},
  volume    = {4},
  journal   = {Cancer \& Metabolism},
  number    = {6},
  doi       = {10.1186/s40170-016-0146-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145905},
  year      = {2016},
  abstract  = {Background Enhanced macromolecule biosynthesis is integral to growth and proliferation of cancer cells. Lipid biosynthesis has been predicted to be an essential process in cancer cells. However, it is unclear which enzymes within this pathway offer the best selectivity for cancer cells and could be suitable therapeutic targets. Results Using functional genomics, we identified stearoyl-CoA desaturase (SCD), an enzyme that controls synthesis of unsaturated fatty acids, as essential in breast and prostate cancer cells. SCD inhibition altered cellular lipid composition and impeded cell viability in the absence of exogenous lipids. SCD inhibition also altered cardiolipin composition, leading to the release of cytochrome C and induction of apoptosis. Furthermore, SCD was required for the generation of poly-unsaturated lipids in cancer cells grown in spheroid cultures, which resemble those found in tumour tissue. We also found that SCD mRNA and protein expression is elevated in human breast cancers and predicts poor survival in high-grade tumours. Finally, silencing of SCD in prostate orthografts efficiently blocked tumour growth and significantly increased animal survival. Conclusions Our data implicate lipid desaturation as an essential process for cancer cell survival and suggest that targeting SCD could efficiently limit tumour expansion, especially under the metabolically compromised conditions of the tumour microenvironment.},
  language  = {en}
}
@article{GattoSchulzeNielsen2016,
  author    = {Gatto, Francesco and Schulze, Almut and Nielsen, Jens},
  title     = {Systematic Analysis Reveals that Cancer Mutations Converge on Deregulated Metabolism of Arachidonate and Xenobiotics},
  series = {Cell Reports},
  volume    = {16},
  journal   = {Cell Reports},
  number    = {3},
  doi       = {10.1016/j.celrep.2016.06.038},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164814},
  pages     = {878-895},
  year      = {2016},
  abstract  = {Mutations are the basis of the clonal evolution of most cancers. Nevertheless, a systematic analysis of whether mutations are selected in cancer because they lead to the deregulation of specific biological processes independent of the type of cancer is still lacking. In this study, we correlated the genome and transcriptome of 1,082 tumors. We found that nine commonly mutated genes correlated with substantial changes in gene expression, which primarily converged on metabolism. Further network analyses circumscribed the convergence to a network of reactions, termed AraX, that involves the glutathione- and oxygen-mediated metabolism of arachidonic acid and xenobiotics. In an independent cohort of 4,462 samples, all nine mutated genes were consistently correlated with the deregulation of AraX. Among all of the metabolic pathways, AraX deregulation represented the strongest predictor of patient survival. These findings suggest that oncogenic mutations drive a selection process that converges on the deregulation of the AraX network.},
  language  = {en}
}