c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism

Gao, Ping; Tchernyshyov, Irina; Chang, Tsung Cheng; Lee, Yun Sil; Kita, Kenji; Ochi, Takafumi; Zeller, Karen; Marzo, Angelo M. De; Eyk, Jennifer E. Van; Mendell, Joshua T.; Dang, Chi V.

doi:10.1038/nature07823

Cited by 1,885 publications

(1,778 citation statements)

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“…The links to metabolism for p53 loss, PI3K/AKT signaling and MYC were investigated with the focus on specific metabolic pathways; i.e. MYC induces glutaminase and proline synthesis via miR-23a/b [187,188], the PI3K/AKT pathway up-regulates FASN expression [189,190], and p53 loss induces mitochondrial aconitase expression [191]. The role of the androgen receptor in the induction of a mixed Warburg phenotype was more globally assessed.…”

Section: Genetic Drivers Signaling and Microenvironment In Prostatementioning

confidence: 99%

Organ-Specific Cancer Metabolism and Its Potential for Therapy

Elia

Schmieder

Christen

et al. 2015

Handbook of Experimental Pharmacology

101

104

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KEYWORDS:Cancer metabolism, metabolic therapy, tissue specific metabolism, genetic drivers, epigenetic drivers, microenvironment, Warburg effect, reverse Warburg effect, mixed Warburg effect, triple-negative breast cancer, estrogen receptor positive breast cancer; prostate cancer, liver cancer, gluconeogenesis, fatty acid metabolism, glucose metabolism, glutamine metabolism, serine metabolism, metabolic normalization, metabolic depletion ABSTRACTTargeting the metabolism of cancer cells has the potential to lead to major advances in tumor therapy. Numerous promising metabolic drug targets have been identified. Yet, it has emerged that there is no singular metabolism that defines the oncogenic state of the cell. Rather, the metabolism of cancer cells is a function of the requirements of a tumor. Hence, the tissue of origin, the (epi)genetic drivers, aberrant signaling, and the microenvironment all together define these metabolic requirements. In this chapter we discuss in light of (epi)genetic, signaling, and environmental factors the diversity in cancer metabolism based on triple-negative and estrogen receptor positive breast cancer, early and late stage prostate cancer, and liver cancer. These types of cancer all display distinct and partially opposing metabolic behaviors (e.g. Warburg versus reverse Warburg metabolism). Yet, for each of the cancers their distinct metabolism supports the oncogenic phenotype. Finally, we will assess the therapeutic potential of metabolism based on the concepts of metabolic normalization and metabolic depletion.

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Section: Genetic Drivers Signaling and Microenvironment In Prostatementioning

confidence: 99%

Organ-Specific Cancer Metabolism and Its Potential for Therapy

Elia

Schmieder

Christen

et al. 2015

Handbook of Experimental Pharmacology

101

104

View full text Add to dashboard Cite

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“…In fact, ammonia levels in the interstitial fluid of xenografts were found to reach 5 mM, a 10-fold increase over physiological values (Eng et al, 2010), and it has long been known that neoplastic cells overexpress glutaminase along with tumor growth and dedifferentiation (Knox et al, 1969). Increased glutamine uptake and utilization are powered by MYC (Gao et al, 2009). Interestingly, ammonia derived from glutamine oxidation enhances cell viability in the tumor microenvironment, acting as a diffusible activator of autophagy (Eng et al, 2010), a process responsible for damaged protein and organelle turnover that serves as a defense against nutrient deprivation and hypoxia (Mizushima et al, 2008).…”

Section: Bioenergetics and The Tumor Microenvironmentmentioning

confidence: 99%

Metabolic reprogramming of the tumor

2012

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Cancer is classically considered as a genetic and, more recently, epigenetic multistep disease. Despite seminal studies in the 1920s by Warburg showing a characteristic metabolic pattern for tumors, cancer bioenergetics has often been relegated to the backwaters of cancer biology. This review aims to provide a historical account on cancer metabolism research, and to try to integrate and systematize the metabolic strategies in which cancer cells engage to overcome selective pressures during their inception and evolution. Implications of this renovated view on some common concepts and in therapeutics are also discussed.

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“…Indeed, glucose is not the only molecule that tumor cells require to grow. For instance, oncogenic myc promotes the use of the amino acid glutamine, which cells can use to produce not only proteins but also ATP and nucleic acids (DeBerardinis et al, 2007;Gao et al, 2009). Growing cells require to synthesize new lipids, nucleic acids and proteins, which means that inhibition of many metabolic pathways, such as fatty acid synthesis or nucleotide synthesis, could promote tumor cell death.…”

Section: Metabolic Transformation: Cancer's Friend and Foementioning

confidence: 99%

Sugar-free approaches to cancer cell killing

et al. 2010

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Tumors show an increased rate of glucose uptake and utilization. For this reason, glucose analogs are used to visualize tumors by the positron emission tomography technique, and inhibitors of glycolytic metabolism are being tested in clinical trials. Upregulation of glycolysis confers several advantages to tumor cells: it promotes tumor growth and has also been shown to interfere with cell death at multiple levels. Enforcement of glycolysis inhibits apoptosis induced by cytokine deprivation. Conversely, antiglycolytic agents enhance cell death induced by radio-and chemotherapy. Synergistic effects are likely due to regulation of the apoptotic machinery, as glucose regulates activation and levels of proapoptotic BH3-only proteins such as Bim, Bad, Puma and Noxa, as well as the antiapoptotic Bcl-2 family of proteins. Moreover, inhibition of glucose metabolism sensitizes cells to death ligands. Glucose deprivation and antiglycolytic drugs induce tumor cell death, which can proceed through necrosis or through mitochondrial or caspase-8-mediated apoptosis. We will discuss how oncogenic pathways involved in metabolic stress signaling, such as p53, AMPK (adenosine monophosphate-activated protein kinase) and Akt/mTOR (mammalian target of rapamycin), influence sensitivity to inhibition of glucose metabolism. Finally, we will analyze the rationale for the use of antiglycolytic inhibitors in the clinic, either as single agents or as a part of combination therapies.

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c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism

Cited by 1,885 publications

References 31 publications

Organ-Specific Cancer Metabolism and Its Potential for Therapy

Organ-Specific Cancer Metabolism and Its Potential for Therapy

Metabolic reprogramming of the tumor

Sugar-free approaches to cancer cell killing

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