@article{41fcb435f90e4324a6675386c5074dda,
title = "Metabolic Diversity in Human Non-Small Cell Lung Cancer Cells",
abstract = "Intermediary metabolism in cancer cells is regulated by diverse cell-autonomous processes, including signal transduction and gene expression patterns, arising from specific oncogenotypes and cell lineages. Although it is well established that metabolic reprogramming is a hallmark of cancer, we lack a full view of the diversity of metabolic programs in cancer cells and an unbiased assessment of the associations between metabolic pathway preferences and other cell-autonomous processes. Here, we quantified metabolic features, mostly from the 13C enrichment of molecules from central carbon metabolism, in over 80 non-small cell lung cancer (NSCLC) cell lines cultured under identical conditions. Because these cell lines were extensively annotated for oncogenotype, gene expression, protein expression, and therapeutic sensitivity, the resulting database enables the user to uncover new relationships between metabolism and these orthogonal processes. Metabolic reprogramming influences therapeutic sensitivity in cancer, but the scope of metabolic diversity among cancer cells is unknown. Chen et al. characterized metabolic phenotypes in over 80 non-small cell lung cancer cell lines and then used genomics, transcriptomics, proteomics, and therapeutic sensitivities to uncover relationships between metabolism and orthogonal processes.",
keywords = "C stable isotope labeling, cancer metabolism, cell lines, gene expression, glucose, glutamine, non-small cell lung cancer, oncogenotypes, protein expression, therapeutic sensitivity",
author = "Chen, {Pei Hsuan} and Ling Cai and Kenneth Huffman and Chendong Yang and Jiyeon Kim and Brandon Faubert and Lindsey Boroughs and Bookyung Ko and Jessica Sudderth and McMillan, {Elizabeth A.} and Luc Girard and Dong Chen and Michael Peyton and Shields, {Misty D.} and Bo Yao and Shames, {David S.} and Kim, {Hyun Seok} and Brenda Timmons and Ikuo Sekine and Rebecca Britt and Stephanie Weber and Byers, {Lauren A.} and Heymach, {John V.} and Jing Chen and White, {Michael A.} and Minna, {John D.} and Guanghua Xiao and DeBerardinis, {Ralph J.}",
note = "Funding Information: We thank Maithili Dalvi, Robin Frink, Rachel Greer, and Sunny Zachariah for generating compound sensitivity data. We thank Julia Kozlitina for advice about data analysis. Genentech provided DNA methylation data. L.C. was supported by an American Association for Cancer Research Basic Cancer Research Fellowship (15 40 01 CAIL). R.J.D. is supported by the Howard Hughes Medical Institute, National Cancer Institute (NCI; R35CA22044901), Cancer Prevention and Research Institute of Texas (CPRIT, RP160089), Robert A. Welch Foundation (grant I-1733), Robert L. Moody, Sr. Faculty Scholar Endowment, and Joel B. Steinberg, M.D. Chair in Pediatrics. J.D.M. is supported by CPRIT (RP160652) and NCI (P50CA70907), which also provided cell line resources for this project. Conceptualization, R.J.D. and P.-H.C.; Methodology, P.-H.C.; Formal Analysis, L.C. E.A.M. and H.S.K.; Investigation, P.-H.C, C.Y. J.K. B.F. L.B. B.K. J.S. D.C. J.C. and M.D.S.; Resources, M.P. B.T. I.S. R.B. S.W. K.H. L.G. B.Y. D.S.S, L.A.B. J.V.H. and J.D.M; Data Curation, L.C. and L.G.; Writing – Original Draft, L.C. P.-H.C. and R.J.D.; Writing – Review & Editing L.C. and R.J.D.; Supervision, R.J.D. G.X. J.D.M. and M.A.W.; Funding Acquisition, R.J.D. R.J.D. is an advisor for Agios Pharmaceuticals. J.D.M. receives licensing fees from the NCI and UT Southwestern to distribute cell lines. J.V.H. is an advisor for AstraZeneca, Boehringer Ingelheim, Exelixis, Genentech, GSK, Guardant Health, Hengrui, Lilly, Novartis, Spectrum, EMD Serono, and Syntal; receives research support from AstraZeneca, Bayer, GlaxoSmithKline, Spectrum, and Takeda; and receives royalty and licensing fees from Spectrum, and Biotree. L.A.B. receives research support from AbbVie, AstraZeneca, GenMab, Tolero Pharmaceuticals, and Sierra Oncology. M.A.W. and E.A.M. are currently employed by Pfizer Inc. Funding Information: We thank Maithili Dalvi, Robin Frink, Rachel Greer, and Sunny Zachariah for generating compound sensitivity data. We thank Julia Kozlitina for advice about data analysis. Genentech provided DNA methylation data. L.C. was supported by an American Association for Cancer Research Basic Cancer Research Fellowship ( 15 40 01 CAIL ). R.J.D. is supported by the Howard Hughes Medical Institute , National Cancer Institute (NCI; R35CA22044901 ), Cancer Prevention and Research Institute of Texas ( CPRIT, RP160089 ), Robert A. Welch Foundation (grant I-1733 ), Robert L. Moody, Sr. Faculty Scholar Endowment , and Joel B. Steinberg, M.D. Chair in Pediatrics . J.D.M. is supported by CPRIT ( RP160652 ) and NCI ( P50CA70907 ), which also provided cell line resources for this project. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = dec,
day = "5",
doi = "10.1016/j.molcel.2019.08.028",
language = "English (US)",
volume = "76",
pages = "838--851.e5",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "5",
}