Fundamentals of cancer metabolism

DeBerardinis, Ralph J.; Chandel, Navdeep S.

doi:10.1126/sciadv.1600200

Cited by 2,301 publications

(2,156 citation statements)

References 204 publications

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“…Although Warburg proposed that altered metabolism was the cause of cancer, it is now known that in most cases it is a supporting outcome of transformation driven by other mechanisms. A key function of metabolic reprogramming in cancer cells is to provide biosynthetic intermediates to support proliferation [5,6]. In the glycolytic pathway, conversion of phosphoenolpyruvate to pyruvate is slowed by expression of the low activity pyruvate kinase M2 (PKM2) isoform.…”

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confidence: 99%

A Tale of Two Glutaminases: Homologous Enzymes with Distinct Roles in Tumorigenesis

2017

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Many cancer cells exhibit an altered metabolic phenotype, in which glutamine consumption is upregulated relative to healthy cells. This metabolic reprogramming often depends upon mitochondrial glutaminase activity, which converts glutamine to glutamate, a key precursor for biosynthetic and bioenergetic processes. Two isozymes of glutaminase exist, a kidney-type (GLS) and a liver-type enzyme (GLS2 or LGA). While a majority of studies have focused on GLS, here we summarize key findings on both glutaminases, describing their structure and function, their roles in cancer and pharmacological approaches to inhibiting their activities.

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confidence: 99%

A Tale of Two Glutaminases: Homologous Enzymes with Distinct Roles in Tumorigenesis

2017

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“…For example, in order for cancer cells to survive glucose deprivation, glutamate dehydrogenase activity increases to support the synthesis of TCA cycle intermediates that can be utilized for macromolecular and nucleotide synthesis (36,37). More salient for the topic at hand, glutamine metabolism is critically important for the production of glutathione and NADPH which both function to detoxify ROS in a fashion that is required for cancer cell survival (19,(37)(38)(39)(40)(41)(42)(43)(44). Moreover, certain types of cancers appear to have a specific mechanism to utilize glutamine to effectuate their progression.…”

Section: Mitochondrial and Amino Acid Metabolismmentioning

confidence: 99%

Mechanisms of redox metabolism and cancer cell survival during extracellular matrix detachment

Hawk

Schafer

2018

Journal of Biological Chemistry

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Abstract:Non-transformed cells that become detached from the extracellular matrix (ECM) undergo dysregulation of redox homeostasis and cell death. In contrast, cancer cells often acquire the ability to mitigate programmed cell death pathways and recalibrate the redox balance to survive after ECM detachment, facilitating metastatic dissemination. Accordingly, recent studies of the mechanisms by which cancer cells overcome ECM detachment-induced metabolic alterations have focused on mechanisms in redox homeostasis. The insights into these mechanisms may inform the development of therapeutics that manipulate redox homeostasis to eliminate ECMdetached cancer cells. Here, we review how ECM-detached cancer cells balance redox metabolism for survival. Introduction:

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“…SCC9β6KDFyn cells are the most potentiated to initiate EMT (7,14). Due to the close relationship between tumor hypoxia and EMT, we used the SCC9β6KDFyn cells to study hypoxia (7,20,21).…”

Section: Mcs Formation Results In Impaired Expression Of Vimentinmentioning

confidence: 99%

“…Tumor-hypoxia can alter vascularization and help the acquisition of epithelial-to-mesenchymal transition phenotype, which can result in enhanced cell mobility and metastasis (15). Hypoxia in the tumor microenvironment may also play a role in conferring resistance to therapy and it is currently a focus of cancer treatment since many solid tumors display an additional growth advantage through their ability to survive in a hypoxic environment (14). HIF1α is up-regulated by oxygen deprivation and is associated with increased patient mortality in several cancer types (15).…”

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Multicellular Spheroids as a Model for Hypoxia-induced EMT

Lee

Siu

Ramos

2016

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Abstract. Oral cancer is aggressive and invasive. The 5-year survival rate is around 50% and has not improved in over 50 years. One-third of oral cancer patients develop local and/or regional tumor recurrence following treatment. We continue to use our multicellular spheroid (MCS) model to better understand how the extracellular matrix contributes to epithelial to mesenchymal transition and how hypoxia contributes to the progression of oral squamous cell carcinoma (SCC).Oral cancer is the sixth most common type of cancer in the world. In the United States, 37,000 new cases are diagnosed annually and each year 8,000 individuals die from this disease (1). Squamous cell carcinoma (SCC) makes up 96% of all oral cancers (2). Despite advances in treatment, the prognosis for oral SCC has not improved in over 50 years.The 5-year survival rate for oral SCC is approximately 50% (3). The poor prognosis of SCC is due to invasion and local recurrence. Interactions between primary SCC cells and the surrounding extracellular matrix (ECM) facilitate invasion. As a tumor grows its available resources, including oxygen availability, become extremely limited which may affect tumor cell behavior. In this study, we aimed to determine the effect of hypoxia on EMT in OSCC spheroids.SCC cells undergo a transformative process known as epithelial-mesenchymal transition (EMT). EMT is a process by which epithelial cells lose their cell polarity, decrease cellcell adhesion, and gain migratory and invasive properties. EMT involves changes in expression, distribution, and function of a number of proteins for cells to transition between the epithelial and mesenchymal phenotype. During EMT, Ecadherin expression is lost; thereby disrupting desmosomes, promoting invasion and de-differentiation (4). N-cadherin acquisition also promotes invasive SCC behavior (4,5).Previous studies show that the αvβ6 integrin, an epithelial specific integrin, is instrumental to EMT in colorectal and oral cancer (6, 7). The αvβ6 integrin is an epithelial-specific adhesion receptor normally not expressed in oral keratinocytes. However, upon wounding or neoplastic transformation, αvβ6 is highly expressed by the same keratinocytes. The αvβ6 integrin is an adhesion receptor for fibronectin (FN) and tenascin-C, and also activates TGFβ1 (8, 9). Binding of αvβ6 integrin to FN results in the activation of FYN kinase in oral SCC. The activation of FYN kinase promotes activation of RAF/MAPK which induces EMT (10). Our laboratory demonstrated that expression of the full-length β6 subunit is required for maintenance of the mesenchymal phenotype thus promoting EMT (7).Keratins are the major structural components of the epithelial cell cytoskeleton and play a strategic role in their architectural integrity (11). It has been shown that gene mutations in keratin are responsible for a large number of inherited skin disorders thus, reinforcing their role in structural integrity of the epithelium (11). In addition to cytoskeletal changes, it is a common process for the ECM to undergo a...

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Fundamentals of cancer metabolism

Abstract: Researchers provide a conceptual framework to understand current knowledge of the fundamentals of cancer metabolism.

Cited by 2,301 publications

References 204 publications

A Tale of Two Glutaminases: Homologous Enzymes with Distinct Roles in Tumorigenesis

A Tale of Two Glutaminases: Homologous Enzymes with Distinct Roles in Tumorigenesis

Mechanisms of redox metabolism and cancer cell survival during extracellular matrix detachment

Multicellular Spheroids as a Model for Hypoxia-induced EMT

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