Cancer Cell Metabolism: One Hallmark, Many Faces

Cantor, Jason R.; Sabatini, David M.

doi:10.1158/2159-8290.cd-12-0345

Cited by 815 publications

(752 citation statements)

References 156 publications

(191 reference statements)

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“…Because it has been speculated that some SCLCs arise from neuroendocrine cells ( 4 ), the upregulation of neural-related genes upon MAX reconstitution may refl ect the activation of prodifferentiation programs. Genes encoding glycolysis enzymes (e.g., LDHA , HK2 , PDK1 , PKM2 , and PGK1 ) are targets of MYC and are commonly overexpressed in cancer cells ( 18 ). Conversely, the levels of these glycolysis-related genes were lower in the sh BRG1 cells than in the control cells.…”

Section: Research Articlementioning

confidence: 97%

“…4A ; refs. 17,18 ). Because SCLCs have neuroendocrine features ( 6 , 11 ), the upregulation of neural-related genes upon MAX reconstitution possibly refl ects the activation of prodifferentiation programs.…”

Section: Max Requires Brg1 To Activate Neuroendocrine Transcriptionalmentioning

confidence: 99%

“…The reconstitution of MAX in SCLC cells triggered the expression of neural-related and glycolysis/carbohydrate metabolism-related transcripts, some of which are wellestablished targets of MYC ( 17,18 ). Because it has been speculated that some SCLCs arise from neuroendocrine cells ( 4 ), the upregulation of neural-related genes upon MAX reconstitution may refl ect the activation of prodifferentiation programs.…”

Section: Research Articlementioning

confidence: 99%

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MAX Inactivation in Small Cell Lung Cancer Disrupts MYC–SWI/SNF Programs and Is Synthetic Lethal with BRG1

et al. 2014

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Our knowledge of small cell lung cancer (SCLC) genetics is still very limited, amplifi cation of L-MYC , N-MYC , and C-MYC being some of the well-established gene alterations. Here, we report our discovery of tumor-specifi c inactivation of the MYC-associated factor X gene, MAX , in SCLC. MAX inactivation is mutually exclusive with alterations of MYC and BRG1 , the latter coding for an ATPase of the switch/sucrose nonfermentable (SWI/SNF) complex. We demonstrate that BRG1 regulates the expression of MAX through direct recruitment to the MAX promoter, and that depletion of BRG1 strongly hinders cell growth, specifi cally in MAX-defi cient cells, heralding a synthetic lethal interaction. Furthermore, MAX requires BRG1 to activate neuroendocrine transcriptional programs and to upregulate MYC targets, such as glycolysis-related genes. Finally, inactivation of the MAX dimerization protein, MGA, was also observed in both non-small cell lung cancer and SCLC. Our results provide evidence that an aberrant SWI/SNF-MYC network is essential for lung cancer development. SIGNIFICANCE:We discovered that the MYC-associated factor X gene, MAX , is inactivated in SCLCs. Furthermore, we revealed a preferential toxicity of the inactivation of the chromatin remodeler BRG1 in MAX-defi cient lung cancer cells, which opens novel therapeutic possibilities for the treatment of patients with SCLC with MAX-defi cient tumors. Cancer Discov; 4(3);[292][293][294][295][296][297][298][299][300][301][302][303]

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Section: Research Articlementioning

confidence: 97%

Section: Max Requires Brg1 To Activate Neuroendocrine Transcriptionalmentioning

confidence: 99%

Section: Research Articlementioning

confidence: 99%

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MAX Inactivation in Small Cell Lung Cancer Disrupts MYC–SWI/SNF Programs and Is Synthetic Lethal with BRG1

et al. 2014

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“…The citrate required derives from glucose and glutamine, either by condensation of acetyl-CoA and oxaloacetate, or by mitochondrial isocitrate dehydrogenase (IDH2)-mediated conversion of a-ketoglutarate [25]. Lipid metabolism is also deregulated in some cancers and can contribute to their proliferative metabolism [29]. Finally, mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 seem to play important roles especially in gliomas and leukaemias ( [34]; see [35]).…”

Section: Overview Of the Major Metabolic Changes In Cancer Cellsmentioning

confidence: 99%

Interactions of ion transporters and channels with cancer cell metabolism and the tumour microenvironment

Andersen

Moreira

Pedersen

2014

Phil. Trans. R. Soc. B

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Major changes in intra-and extracellular pH homoeostasis are shared features of most solid tumours. These changes stem in large part from the metabolic shift of most cancer cells towards glycolytic metabolism and other processes associated with net acid production. In combination with oncogenic signalling and impact from factors in the tumour microenvironment, this upregulates acid-extruding plasma membrane transport proteins which maintain intracellular pH normal or even more alkaline compared with that of normal cells, while in turn acidifying the external microenvironment. Mounting evidence strongly indicates that this contributes significantly to cancer development by favouring e.g. cancer cell migration, invasion and chemotherapy resistance. Finally, while still under-explored, it seems likely that non-cancer cells in the tumour microenvironment also exhibit altered pH regulation and that this may contribute to their malignant properties. Thus, the physical tumour microenvironment and the cancer and stromal cells within it undergo important reciprocal interactions which modulate the tumour pH profile, in turn severely impacting on the course of cancer progression. Here, we summarize recent knowledge of tumour metabolism and the tumour microenvironment, placing it in the context of tumour pH regulation, and discuss how interfering with these properties may be exploited clinically.

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“…A switch from mitochondrial oxidative phosphorylation (OXPHOS) to glycolytic metabolism, recognized as “Warburg effect,” is a common strategy used by cancer cells to overcome their bioenergetics needs 9, 10. This metabolic reprogramming provides tumour cells with advantages necessary for sustaining their high proliferation rates, such as the rapid generation of ATP and intermediates for the synthesis of fatty acids, nucleotides and amino acids 11.…”

Section: Introductionmentioning

confidence: 99%

Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells

Pereira

Teixeira

Sampaio‐Marques

et al. 2018

J Cellular Molecular Medi

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Acute myeloid leukaemia (AML) comprises a heterogeneous group of hematologic neoplasms characterized by diverse combinations of genetic, phenotypic and clinical features representing a major challenge for the development of targeted therapies. Metabolic reprogramming, mainly driven by deregulation of the nutrient‐sensing pathways as AMPK, mTOR and PI3K/AKT, has been associated with cancer cells, including AML cells, survival and proliferation. Nevertheless, the role of these metabolic adaptations on the AML pathogenesis is still controversial. In this work, the metabolic status and the respective metabolic networks operating in different AML cells (NB‐4, HL‐60 and KG‐1) and their impact on autophagy and survival was characterized. Data show that whereas KG‐1 cells exhibited preferential mitochondrial oxidative phosphorylation metabolism with constitutive co‐activation of AMPK and mTORC1 associated with increased autophagy, NB‐4 and HL‐60 cells displayed a dependent glycolytic profile mainly associated with AKT/mTORC1 activation and low autophagy flux. Inhibition of AKT is disclosed as a promising therapeutical target in some scenarios while inhibition of AMPK and mTORC1 has no major impact on KG‐1 cells’ survival. The results highlight an exclusive metabolic profile for each tested AML cells and its impact on determination of the anti‐leukaemia efficacy and on personalized combinatory therapy with conventional and targeted agents.

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Cancer Cell Metabolism: One Hallmark, Many Faces

Cited by 815 publications

References 156 publications

MAX Inactivation in Small Cell Lung Cancer Disrupts MYC–SWI/SNF Programs and Is Synthetic Lethal with BRG1

MAX Inactivation in Small Cell Lung Cancer Disrupts MYC–SWI/SNF Programs and Is Synthetic Lethal with BRG1

Interactions of ion transporters and channels with cancer cell metabolism and the tumour microenvironment

Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells

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