Environment impacts the metabolic dependencies of Ras-driven non-small cell lung cancer

By S. Davidson, T. Papagiannakopoulos, B. Olenchock, Julia Heyman, Mark A Keibler, Alba Luengo, Matthew R. Bauer, Abhishek K. Jha, James P. O’Brien, K. Pierce and 10 more. Cell Metabolism, 2016

676 citations recorded by the source corpus.

SUMMARY Cultured cells convert glucose to lactate and glutamine is the major source of tricarboxylic acid (TCA) cycle carbon, but whether the same metabolic phenotype is found in tumors is less studied. We infused mice with lung cancers with isotope-labeled glucose or glutamine and compared the fate of these nutrients in tumor and normal tissue. As expected, lung tumors exhibit increased lactate production from glucose. However, glutamine utilization by both lung tumors and normal lung was minimal, with lung tumors showing increased glucose contribution to the TCA cycle relative to normal lung tissue. Deletion of enzymes involved in glucose oxidation demonstrates that glucose carbon contribution to the TCA cycle is required for tumor formation. These data suggest that understanding nutrient utilization by tumors can predict metabolic dependencies of cancers in vivo. Furthermore, these data argue that the in vivo environment is an important determinant of the metabolic phenotype of cancer cells.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/5e03166df2976949d408eecb5ca681ffd8de2102

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

In Molecular Biology

Citations in the corpus

From Krebs to Clinic: Glutamine Metabolism to Cancer Therapy (2016, neutral): “BPTES inhibition of hGA(124-551), a truncated form of human kidneytype glutaminase.”
Glutaminolysis: A Hallmark of Cancer Metabolism. (2017, background): “Similarly, Rasdriven lung cancer cells showed glutamine anaplerosis in vitro, but not in vivo in animal models (160).”
Understanding the intersections between metabolism and cancer biology (2017, neutral): “Recent data indicate that PDH is active and required by some tumors (Davidson et al., 2016b; Hensley et al., 2016), tempering hope that further activating the enzyme will be therapeutically useful.”
Metabolic heterogeneity in human lung tumors (2016, neutral): “PDH was also recently shown to be required for tumor cell survival and/or growth in a KRAS-driven mouse model of lung cancer, arguing that this enzyme is crucial for cancer cells in the lung microenvironment (Davidson et al., 2016).”
Mitochondrial metabolism and cancer (2017, background): “revealed that not only the oncogenic driver, but also the tumor microenvironment (in particular tissue of origin) influence the metabolic profile of malignant cells [117-119].”
Lactate metabolism in human lung tumors (2017, neutral): “The metabolic fates of glucose in FDG-PET-positive tumors and the extent to which other fuels complement glucose utilization in these tumors are areas of active study (Davidson et al., 2016; Fan et al., 2009; Hensley et al., 2016; Mashimo et al., 2014).”
Targeting Metabolism for Cancer Therapy (2017, background): “…chemotherapies targeting metabolism for decades, and environment can also influence the efficacy of drugs targeting DHODH, mitochondrial complex I, and glutaminase (Davidson et al., 2016; Gui et al., 2016; Marin-Valencia et al., 2012; Sellers et al., 2015; Sykes et al., 2016; Tardito et al., 2015).”