Metabolic Diversity in Human Non-Small Cell Lung Cancer Cells

Pei Hsuan Chen, Ling Cai, Kenneth Huffman, Chendong Yang, Jiyeon Kim, Brandon Faubert, Lindsey Boroughs, Bookyung Ko, Jessica Sudderth, Elizabeth A. McMillan, Luc Girard, Dong Chen, Michael Peyton, Misty D. Shields, Bo Yao, David S. Shames, Hyun Seok Kim, Brenda Timmons, Ikuo Sekine, Rebecca BrittStephanie Weber, Lauren A. Byers, John V. Heymach, Jing Chen, Michael A. White, John D. Minna, Guanghua Xiao, Ralph J. DeBerardinis

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)838-851.e5
JournalMolecular cell
Volume76
Issue number5
DOIs
StatePublished - Dec 5 2019

Keywords

  • C stable isotope labeling
  • cancer metabolism
  • cell lines
  • gene expression
  • glucose
  • glutamine
  • non-small cell lung cancer
  • oncogenotypes
  • protein expression
  • therapeutic sensitivity

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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