The Metabolic Profile of Tumors Depends on both the Responsible Genetic Lesion and Tissue Type

By M. Yuneva, Teresa W.-M. Fan, Thaddeus David Allen, R. Higashi, D. Ferraris, T. Tsukamoto, J. Matés, F. J. Alonso, Chunmei Wang, Youngho Seo and 2 more. Cell Metabolism, 2012

634 citations recorded by the source corpus.

SUMMARY The altered metabolism of tumors has been considered a target for anti-cancer therapy. However, the relationship between distinct tumor-initiating lesions and anomalies of tumor metabolism in vivo has not been addressed. We report that MYC-induced mouse liver tumors significantly increase both glucose and glutamine catabolism, whereas MET-induced liver tumors use glucose to produce glutamine. Increased glutamine catabolism in MYC-induced liver tumors is associated with decreased levels of glutamine synthetase (Glul) and the switch from Gls2 to Gls1 glutaminase. In contrast to liver tumors, MYC-induced lung tumors display increased expression of both Glul and Gls1 and accumulate glutamine. We also show that inhibition of Gls1 kills cells that over-express MYC and catabolize glutamine. Our results suggest that the metabolic profiles of tumors are likely to depend on both the genotype and tissue of origin and have implications regarding the design of therapies targeting tumor metabolism.

Subfields: Biotechnology, Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/4863cd168458eaa5cb2b47ac1558830c0e126af1

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Citations in the corpus

The return of metabolism: biochemistry and physiology of the pentose phosphate pathway (2014, background): “Observed changes in metabolism are in no way ‘trivial’, indeed can be quite specific dependent on both the responsible genetic lesion and tumour tissue type (Yuneva et al., 2012).”
Understanding the intersections between metabolism and cancer biology (2017, neutral): “A requirement for glutamine metabolism has been observed in many cancer types (Altman et al., 2016), but both tissue of origin and genetics contribute to this phenotype (Yuneva et al., 2012).”
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].”
MYC, metabolism, cell growth, and tumorigenesis. (2013, background): “In growing cells, a significant amount of pyruvate is converted to lactate, a phenomenon known as aerobic glycolysis or the Warburg effect (Cantor and Sabatini 2012; Zaidi et al. 2012).”
Glutaminolysis: A Hallmark of Cancer Metabolism. (2017, background): “Moreover, glioma animal models showed de novo glutamine synthesis from glutamate by GS, as observed in Myc-induced lung tumors (157, 158, 161).”
HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. (2013, neutral): “…will respond to inhibition of particular metabolic pathways, including the use of algorithms that infer metabolic phenotypes from RNA/protein expression data (112), metabolomic profiling techniques (113), stable isotope–based metabolic analysis (114, 115), and functional genomic strategies (116).”
Cancer Cell Metabolism: One Hallmark, Many Faces (2012, background): “In another study, the interplay between oncogenic alteration and tumor tissue of origin was shown to influence a differential utilization of glucose and glutamine as proliferative fuels (156).”