Shorthouse, David;
Bradley, Jenna;
Critchlow, Susan E;
Bendtsen, Claus;
Hall, Benjamin A;
(2022)
Heterogeneity of the cancer cell line metabolic landscape.
Molecular Systems Biology
, 18
(11)
, Article e11006. 10.15252/msb.202211006.
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Abstract
The unravelling of the complexity of cellular metabolism is in its infancy. Cancer-associated genetic alterations may result in changes to cellular metabolism that aid in understanding phenotypic changes, reveal detectable metabolic signatures, or elucidate vulnerabilities to particular drugs. To understand cancer-associated metabolic transformation, we performed untargeted metabolite analysis of 173 different cancer cell lines from 11 different tissues under constant conditions for 1,099 different species using mass spectrometry (MS). We correlate known cancer-associated mutations and gene expression programs with metabolic signatures, generating novel associations of known metabolic pathways with known cancer drivers. We show that metabolic activity correlates with drug sensitivity and use metabolic activity to predict drug response and synergy. Finally, we study the metabolic heterogeneity of cancer mutations across tissues, and find that genes exhibit a range of context specific, and more general metabolic control.
| Type: | Article |
|---|---|
| Title: | Heterogeneity of the cancer cell line metabolic landscape |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.15252/msb.202211006 |
| Publisher version: | https://doi.org/10.15252/msb.202211006 |
| Language: | English |
| Additional information: | © 2022 The Authors. Published under the terms of the CC BY 4.0 license. |
| Keywords: | cancer, heterogeneity, metabolomics, mutation, Humans, Metabolomics, Neoplasms, Mass Spectrometry, Metabolic Networks and Pathways, Cell Line |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10158873 |
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