Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate

By Patrick S. Ward, Craig B. Thompson. Cancer Cell, 2012

3,098 citations recorded by the source corpus.

Cancer metabolism has long been equated with aerobic glycolysis, seen by early biochemists as primitive and inefficient. Despite these early beliefs, the metabolic signatures of cancer cells are not passive responses to damaged mitochondria, but result from oncogene-directed metabolic reprogramming required to support anabolic growth. Recent evidence suggests that metabolites themselves can be oncogenic by altering cell signaling and blocking cellular differentiation. No longer can cancer-associated alterations in metabolism be viewed as an indirect response to cell proliferation and survival signals. We contend that altered metabolism has attained the status of a core hallmark of cancer.

Subfields: Cancer Research, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/9802ecaa29613434cd7f6f7fa0e72b84a26c9d29

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Citations in the corpus

ROS homeostasis and metabolism: a dangerous liason in cancer cells (2016, background): “Oncogenic activation of MYC and KRAS promote increased glucose utilization and addiction in different types of tumors,(134) while also enhancing the mitochondrial-dependent biosynthesis of macromolecules through increased ATP levels and TCA cycle intermediates.(64,135) To replenish the TCA cycle sub”
Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013, background): “The previous paradigm of metabolic regulation argued that metabolic pathways were exclusively controlled through allosteric regulation of metabolic enzymes, either by ATP levels or metabolites themselves (the reactive model) (40).”
Loss of BRCA1 in the cells of origin of ovarian cancer induces glycolysis: A window of opportunity for ovarian cancer chemoprevention (2017, background): “The reliance of cancer cells on aerobic glycolysis, even in the presence of oxygen, is now termed the "Warburg effect" and the reprograming of metabolism in cancer cells has been recognized as a hallmark of cancer (9, 10).”
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Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity (2020, background): “However, this was deemed incorrect as most tumor mitochondria can effectively carry out oxidative phosphorylation and can also rewire their metabolism to promote biosynthesis and survival under stress [160].”
Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses (2015, background): “…Elsevier Inc. 1217 Deregulated anabolic metabolism and increased rates of aerobic glycolysis (i.e., the Warburg effect), glutaminolysis and fatty acid synthesis are cardinal features of most tumor cells that fuels their growth and proliferation (Hanahan and Weinberg, 2011; Ward and Thompson, 2012).”
A cellular perspective on brain energy metabolism and functional imaging. (2015, background): “The PKM2 isoform, which in addition to astrocytes is also enriched in cells displaying sustained aerobic glycolysis such as cancer cells (Ward and Thompson, 2012), can upregulate the glycolytic flux in response to increased energy demands, whereas PKM1, the form expressed in neurons, does not have…”
Cancer Cell Metabolism: One Hallmark, Many Faces (2012, background): “However, it has since been demonstrated that mitochondrial respiration persists in most proliferating cells, and in turn retains its role as the primary source of ATP generation (12, 25).”
The Warburg effect: essential part of metabolic reprogramming and central contributor to cancer progression (2019, background): “…anticipated by Warburg, his supporters and contemporaries (e.g. DeBerardinis et al. 2008; Vander Heiden et al. 2009; Cairns et al. 2011; Mihaylova and Shaw 2011; Ward and Thompson 2012; Amoedo et al. 2013; Soga 2013; Phan et al. 2014; Liberty and Locasale 2016; Bose and Le 2018; Kato et al. 2018).”
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Gene Body Methylation can alter Gene Expression and is a Therapeutic Target in Cancer (2014, background): “Metabolic reprogramming is now considered to be one of cancer’s hallmarks because the metabolites themselves can be oncogenic by altering cell signaling and blocking cellular differentiation (Hanahan and Weinberg, 2011; Ward and Thompson, 2012).”
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