JOURNAL CLUB

Metabolism and Cancer articlesMetabolist: Literature updates for researchers

ASS1 metabolically contributes to the nuclear and cytosolic p53-mediated DNA damage response - Nature MetabolismLim, Adler et al. show that the urea cycle enzyme ASS1 can function in the nucleus to supply fumarate necessary to drive DNA damage responses.

2024.11.18 오현택

ULK1 inhibition overcomes compromised antigen presentation and restores antitumor immunity in LKB1-mutant lung cancer - Nature CancerWong and colleagues show that LKB1-deficient lung tumors are sensitive to autophagy inhibition, which can restore impaired antigen presentation and antitumor immune responses, and propose dual targeting of ULK1 and PD-1 for these tumors.

2024.11.09 곽시우

Unraveling ETC complex I function in ferroptosis reveals a potential ferroptosis-inducing therapeutic strategy for LKB1-deficient cancersMao et al. reveal that pharmacological inhibition of electron transport chain (ETC) complex I reduces ubiquinol levels but activates AMPK, resulting in a limited effect on ferroptosis. They further show that complex I inhibition sensitizes LKB1-AMPK-inactivated cells to ferroptosis and boosts radiation to suppress LKB1-deficient tumor growth by inducing ferroptosis.

2024.11.02 김수진

Metabolic and transcriptomic reprogramming during contact inhibition-induced quiescence is mediated by YAP-dependent and YAP-independent mechanisms - Nature CommunicationsMetabolic changes happening when cells enter quiescence are poorly understood. Here, the authors report that quiescent cells exhibit reduced glycolysis mediated by YAP inhibition and increased mitochondrial activity mediated by pyruvate carrier induced expression.

2024.10.26 남기태

The hexosamine biosynthesis pathway is a targetable liability in KRAS/LKB1 mutant lung cancer - Nature MetabolismA particularly aggressive subtype of lung cancer with mutations in KRAS and LKB1 is shown to depend on increased hexosamine biosynthesis mediated by the enzyme GFPT2.

2024.10.11 오현택

STK11 loss leads to YAP1-mediated transcriptional activation in human KRAS-driven lung adenocarcinoma cell lines - Cancer Gene Therapy

2024.10.05 곽시우

Glycosphingolipid synthesis mediates immune evasion in KRAS-driven cancer - NatureFunctional genomics and lipidomic analyses reveal that sphingolipid synthesis is required for tumour immune evasion and tumour growth in vivo, mediated in part by the impact of glycosphingolipid synthesis on cell surface expression of IFNγ receptors.

2024.09.28 김수진

The kinase TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling - Nature Immunology

Non-canonical NF-κB Antagonizes STING Sensor-Mediated DNA Sensing in Radiotherapy

The role of TBK1 in cancer pathogenesis and anticancer immunity - Journal of Experimental & Clinical Cancer Research

2024.09.21 최은지

Comutations and KRASG12C Inhibitor Efficacy in Advanced NSCLCGenetic coalterations in KEAP1, SMARCA4, and CDKN2A were revealed as major independent determinants of KRASG12C inhibitor clinical outcomes in advanced non–small cell lung cancer that together allow for patient segregation into prognostic subgroups.

2024.09.07 곽시우

Concurrent loss of LKB1 and KEAP1 enhances SHMT-mediated antioxidant defence in KRAS-mutant lung cancer - Nature MetabolismLee et al. identify SHMT and one-carbon metabolism as a metabolic vulnerability conferred by LKB1 and KEAP1 loss in KRAS-mutant lung cancer.

2024.08.19 김수진

IKK promotes cytokine-induced and cancer-associated AMPK activity and attenuates phenformin-induced cell death in LKB1-deficient cellsAMPK activity is stimulated by IKK-mediated phosphorylation in cancer cells and downstream of inflammatory cytokines.

2024.08.12 천경민

Carnosine regulation of intracellular pH homeostasis promotes lysosome-dependent tumor immunoevasion - Nature ImmunologyCarnosine is a mobile buffering metabolite. Here the authors link carnosine accumulation, hypoxia and intracellular pH homeostasis in cancer cells as a mechanism of tumor immune evasion via NFX1 degradation and galectin-9 activity.

2024.08.05 오현택

Frontiers | NF-κBp50 and HDAC1 Interaction Is Implicated in the Host Tolerance to Infection Mediated by the Bacterial Quorum Sensing Signal 2-AminoacetophenoneSome bacterial quorum sensing (QS) small molecules are important mediators of inter-kingdom signaling and impact host immunity. The QS regulated small volati...

2024.07.29 최은지

IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor ProgressionAryl hydrocarbon receptor (AHR) activation by tryptophan (Trp) catabolites enhances tumor malignancy and suppresses anti-tumor immunity. The context s…

2024.07.22 김수진

HDAC3 is critical in tumor development and therapeutic resistance in Kras-mutant non–small cell lung cancerHDAC3 is essential for Kras, Lkb1-dependent lung tumor growth and therapeutic resistance in genetic engineered mouse models.

2024.07.15 천경민

Metabolic rewiring promotes anti-inflammatory effects of glucocorticoids - NatureGlucocorticoids reprogram the mitochondrial metabolism of macrophages, resulting in increased and sustained production of the anti-inflammatory metabolite itaconate and, as a consequence, inhibition of the inflammatory response.

2024. 07. 08 오현택

Vitamin D Receptor Inhibits Nuclear Factor κB Activation by Interacting with IκB Kinase β Protein1,25-Dihydroxyvitamin D (1,25(OH)2D3) is known to suppress NF-κB activity, but the underlying mechanism remains poorly understood. Here we show that t…

The Tumor Suppressor Kinase LKB1 Activates the Downstream Kinases SIK2 and SIK3 to Stimulate Nuclear Export of Class IIa Histone DeacetylasesHistone deacetylases 4 (HDAC4), -5, -7, and -9 form class IIa within the HDAC superfamily and regulate diverse physiological and pathological cellular…

2024.06.17 천경민

A glycolytic metabolite bypasses “two-hit” tumor suppression by BRCA2Knudson’s “two-hit” paradigm posits that carcinogenesis requires inactivation of both copies of an autosomal tumor suppressor gene. Here, we report th…

2024.05.27 오현택

STK11/LKB1 loss of function is associated with global DNA hypomethylation and S-adenosyl-methionine depletion in human lung adenocarcinomaSTK11 (Liver Kinase B1, LKB1) is the fourth-most frequently mutated gene in lung adenocarcinoma, with loss of function observed in up to 30% of all cases. Our previous work identified a 16-gene signature for LKB1 loss of function through mutational and ...

2024.05.20 김수진

Maintaining Iron Homeostasis Is the Key Role of Lysosomal Acidity for Cell ProliferationThe lysosome is an acidic multi-functional organelle with roles in macromolecular digestion, nutrient sensing, and signaling. However, why cells requi…

2024.05.17 이채연

LKB1 drives stasis and C/EBP-mediated reprogramming to an alveolar type II fate in lung cancer - Nature CommunicationsLKB1 tumour suppressor gene is frequently mutated in lung adenocarcinoma. Here the authors show that in genetically engineered mouse models of lung cancer Lkb1 restoration induces growth arrest and drives neoplastic cells toward a more differentiated and less proliferative alveolar type II cell-like state via C/EBP-mediated reprogramming.

2024.05.06 천경민

PKM2 diverts glycolytic flux in dependence on mitochondrial one-carbon cycleBenzarti et al. demonstrate that glycolytic limitation forces cancer cells to rewire their glycolytic flux toward SSP by PKM2 inhibition. PKM2 inhibition is independent of serine and can be reversed by genetic ablation of mitochondrial 1C cycle enzymes. These findings highlight cellular adaptation mechanisms upon limited carbon supply.

2024.04.29 최은지

PKM2 diverts glycolytic flux in dependence on mitochondrial one-carbon cycleBenzarti et al. demonstrate that glycolytic limitation forces cancer cells to rewire their glycolytic flux toward SSP by PKM2 inhibition. PKM2 inhibition is independent of serine and can be reversed by genetic ablation of mitochondrial 1C cycle enzymes. These findings highlight cellular adaptation mechanisms upon limited carbon supply.

2024.04.22 오현택

Gene Signatures of 1,25‐Dihydroxyvitamin D3 Exposure in Normal and Transformed Mammary Cells The Journal of Cellular Biochemistry publishes research in which complex cellular, pathogenic, clinical, or animal model systems are studied by a range of approaches.

2024.04.15 김수진

The AMPK-Related Kinases SIK1 and SIK3 Mediate Key Tumor-Suppressive Effects of LKB1 in NSCLCLack of activation of the AMPK-related kinases SIK1 and SIK3 may be responsible for the tumorigenic effect of LKB1 mutations in non–small cell lung cancer.

2024.03.25 천경민

Phosphorylation of phase‐separated p62 bodies by ULK1 activates a redox‐independent stress response | The EMBO Journal image image NRF2 is a master transcription factor for antioxidant stress that is usually regulated by redox states of KEAP1. This study shows that when ULK1 phosphorylates phase‐separated p62 bodies, they bind KEAP1, leading to NRF2‐...

2024.03.11 최은지

Oncogenic Signaling Pathways in The Cancer Genome AtlasGenetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the exte…

2024.03.04 김수진

A chromatin-based mechanism controls differential regulation of the cytochrome P450 gene Cyp24a1 in renal and non-renal tissuesCytochrome P450 family 27 subfamily B member 1 (CYP27B1) and CYP24A1 function to maintain physiological levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D…

2024.02.26 천경민

Vitamin B5 supports MYC oncogenic metabolism and tumor progression in breast cancer - Nature MetabolismIn this study, Kreuzaler et al. perform zonal analysis to study metabolic heterogeneity in breast cancer and identify the metabolic dependency on pantothenic acid (vitamin B5) in areas of the tumor that show high expression levels of the oncogene MYC. Dietary restriction of vitamin B5 reverses several MYC-driven metabolic changes and hampers tumor progression.

2024.02.19 이지우

Ornithine aminotransferase supports polyamine synthesis in pancreatic cancer - NaturePancreatic ductal adenocarcinoma cells show a specific dependency on ornithine aminotransferase-mediated ornithine synthesis from glutamine, providing an opportunity to develop targeted therapies with minimal toxicity for this cancer.

2024.02.13 나다은

Proteome census upon nutrient stress reveals Golgiphagy membrane receptors - NatureA proteomics analysis demonstrates that, during nutrient stress, mammalian cells prioritize degradation by autophagy of membrane proteins and identifies receptors that mediate this process at the Golgi and also have a role in Golgi remodelling during neuronal differentiation.

2024.02.08 김기태

p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response - Nature CommunicationsLiquid-liquid phase separation of p62/SQSTM1 has been previously described, although the significance in vivo remains unclear. Here the authors show p62 droplets contain ubiquitin, autophagy-related proteins and Keap1 to serve as platform of not only autophagosome formation but also Nrf2 activation.

2024.01.22 최은지

The CREB coactivator CRTC2 promotes oncogenesis in LKB1-mutant non–small cell lung cancerWe identify CRTC2 as a key mediator of LKB1-mutant non–small cell lung cancer.

2024.01.15 김수진

Dependency of human and murine LKB1-inactivated lung cancer on aberrant CRTC-CREB activationTargeting aberrant CRTC-CREB activation blocks the growth of LKB1-inactivated lung cancer.

2024.01.08 오현택

Glucocorticoid receptor Thr524 phosphorylation by MINK1 induces interactions with 14-3-3 protein regulatorsThe glucocorticoid receptor (GR) is a ligand-dependent transcription factor that plays a central role in inflammation. The GR activity is also modulated via protein–protein interactions, including binding of 14-3-3 proteins induced by GR phosphorylation. ...

2024.01.02 천경민

LKB1 controls inflammatory potential through CRTC2-dependent histone acetylationDeregulated inflammation is a critical feature driving the progression of tumors harboring mutations in liver kinase B1 (LKB1). Compton et al. identify a mechanism by which LKB1 epigenetically regulates cellular inflammatory potential through CRTC2-dependent histone acetylation at inflammatory gene loci.

2023.12.18 최은지

Concurrent Mutations in STK11 and KEAP1 Promote Ferroptosis Protection and SCD1 Dependence in Lung CancerConcurrent loss-of-function mutations in STK11 and KEAP1 in lung adenocarcinoma (LUAD) are associated with aggressive tumor growth, resistance to avai…

2023.12.11 오현택

Pan-Cancer Identification of Prognostic-Associated Metabolic PathwaysWhen studying the cancer transcriptome, we found that there is no work that has conducted a global and systematic analysis of the metabolism-related genes and pathways in the cancer transcriptome, especially in connection with cancer prognosis and treatment. ...

2023.11.27 김수진

Glucocorticoid Receptors Drive Breast Cancer Cell Migration and Metabolic Reprogramming via PDK4Abstract. Corticosteroids act on the glucocorticoid receptor (GR; NR3C1) to resolve inflammation and are routinely prescribed to breast cancer patients undergoi

2023.11.20 천경민

Loss of LKB1-NUAK1 signalling enhances NF-κB activity in a spheroid model of high-grade serous ovarian cancer - Scientific Reports

2023.11.13 최은지

Identification of an alternative triglyceride biosynthesis pathway - NatureTriacylglycerols are an energy source produced in humans by DGAT1 and DGAT2, but disrupting these enzymes reveals a noncanonical pathway involving the protein DIESL (formerly TMEM68) and its regulator TMX1, which is important during lipid scarcity.

2023.10.23 천경민

Increased demand for NAD+ relative to ATP drives aerobic glycolysisAerobic glycolysis is associated with proliferation in many biological contexts, yet what drives this phenotype has not been fully explained. Luengo et al. show that cells engage in aerobic glycolysis when the demand for NAD+ exceeds the demand for ATP, which leads to impaired NAD+ regeneration by mitochondrial respiration.

2023.10.16 윤유혁

Pan-cancer analysis of pathway-based gene expression pattern at the individual level reveals biomarkers of clinical prognosisIdentifying biomarkers to predict the clinical outcomes of individual patients is a fundamental problem in clinical oncology. Multiple single-gene bio…

2023.10.09 김수진

Adipocytes reprogram cancer cell metabolism by diverting glucose towards glycerol-3-phosphate thereby promoting metastasis - Nature MetabolismHere Mukherjee et al. characterize the bidirectional communication between adipose tissue and ovarian cancer cells and show that adipocytes instruct cancer cells to divert glycolytic glycerol-3-phosphate towards lipid synthesis, thus promoting metastasis.

2023.10.02 오현택

Determination of glucose deficiency-induced cell death by mitochondrial ATP generation-driven proton homeostasisAbstract. Glucose is one of major nutrients and its catabolism provides energy and/or building bricks for cell proliferation. Glucose deficiency results in cell

2023.09.25 최은지

Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms - Nature CommunicationsGlucocorticoid receptors (GR) are thought to bind DNA as dimers or monomers, to regulate different transcription pathways. Here, the authors perform genome-wide studies on GRs with mutations that impair dimerization and provide evidence that monomeric GRs do not play a significant physiologic role.

2023.09.18 최소연

Nutrient-sensitized screening for drugs that shift energy metabolism from mitochondrial respiration to glycolysis - Nature BiotechnologyMany diseases are characterized by shifts in cellular energy metabolism. Gohil et al. use a quantitative, nutrient-sensitized screen to identify drugs that affect the relative rates of glycolysis and mitochondrial respiration, and demonstrate the protective capacity of an approved antiemetic in models of cardiac and cerebral ischemia.

2023.09.11 오현택

Slow TCA flux and ATP production in primary solid tumours but not metastases - NatureAs solid tumours develop, cancer cells shed energetically expensive tissue-specific functions, enabling uncontrolled growth despite a limited ability to produce ATP.

23.08.29 윤유혁

A pan-cancer metabolic atlas of the tumor microenvironmentTumors are heterogeneous cellular environments with entwined metabolic dependencies. Here, we use a tumor transcriptome deconvolution approach to prof…

23.08.21 김수진

What is cancer metabolism?The uptake and metabolism of nutrients support fundamental cellular process from bioenergetics to biomass production and cell fate regulation. While m…

23.08.14 천경민

AMPK, a Regulator of Metabolism and Autophagy, Is Activated by Lysosomal Damage via a Novel Galectin-Directed Ubiquitin Signal Transduction SystemAMPK is a central regulator of metabolism and autophagy. Here we show how lysosomal damage activates AMPK. This occurs via a hitherto unrecognized sig…

23.08.07 최은지

FEBS PressThe glucocorticoid receptor (GR) is a bona fide ligand-regulated transcription factor. Different methodologies in the pregenomic and genomic era of molecular biological research and recent cutting-ed...

Repression of transcription by the glucocorticoid receptor: A parsimonious model for the genomics eraGlucocorticoids are potent anti-inflammatory drugs that are used to treat an extraordinary range of human disease, including COVID-19, underscoring the ongoing importance of understanding their molecular mechanisms. Early studies of GR signaling led to broad acceptance of models in which glucocorticoid receptor (GR) monomers tether repressively to inflammatory transcription factors, thus abrogating inflammatory gene expression. However, newer data challenge this core concept and present an exciting opportunity to reframe our understanding of GR signaling.

23.07.31 최소연

A non-canonical tricarboxylic acid cycle underlies cellular identity - NatureA non-canonical tricarboxylic acid cycle is required for changes in cell state.

23.07.24 오현택

S-lactoyl modification of KEAP1 by a reactive glycolytic metabolite activates NRF2 signaling-PNAS

Several reactive endogenous metabolites have been shown to activate the NRF2-driven oxidative stress response in mammalian cells. Here, we expand this repertoire of reactive metabolites by showing that pharmacological inhibition of pyruvate kinase, the last step in glycolysis, results in the accumulation of glyceraldehyde 3-phosphate, a metabolite that results in the covalent modification and inactivation of the NRF2 repressor protein KEAP1. This work identifies a nonenzymatically derived posttranslational modification of cysteine, termed S-lactoylation, and further builds upon existing data that glycolysis directly communicates to the KEAP1–NRF2 signaling pathway through reactive metabolite-derived modifications of cysteine.

23.07.10 최민지

Redefining the role of AMPK in autophagy and the energy stress response - Nature CommunicationsAccording to the current understanding in the field, AMPK promotes autophagy by activating ULK1 during energy stress. Here, authors show that AMPK is indeed a negative regulator of ULK1 and it suppresses autophagy in energy depleted cells.

23.06.19 최은지

Flumethasone enhances the efficacy of chemotherapeutic drugs in lung cancer by inhibiting Nrf2 signaling pathwayNuclear factor erythroid-2-related factor 2 (Nrf2), a transcription factor, participates in protecting cells from electrophilic or oxidative stresses …

23.06.12 최민지

Induction of lysosomal and mitochondrial biogenesis by AMPK phosphorylation of FNIP1The energy-sensing protein kinase AMPK also regulates organelle biogenesis.

23.06.04 최은지

Spatial regulation of AMPK signaling revealed by a sensitive kinase activity reporter - Nature CommunicationsAMP activated protein kinase (AMPK) is a master regulator of cellular metabolism, but how AMPK activity is spatiotemporally regulated remains unclear. Here, Schmitt et al develop a sensitive biosensor for AMPK, which they use to uncover mechanisms for AMPK activity in the lysosome and nucleus.

23.05.15 오현택

Repurposed pizotifen malate targeting NRF2 exhibits anti-tumor activity through inducing ferroptosis in esophageal squamous cell carcinoma - Oncogene

23.05.08 최민지

AMPK-dependent phosphorylation of the GATOR2 component WDR24 suppresses glucose-mediated mTORC1 activation - Nature MetabolismDai et al. show that in response to low glucose levels, AMP-activated protein kinase-mediated phosphorylation of WDR24, a component of the GATOR2 complex, leads to suppression of mTORC1 activation.

2023.05.01 최은지

Apollo-NADP+: a spectrally tunable family of genetically encoded sensors for NADP+ - Nature MethodsHomoFRET sensors based on G6PD homodimerization allow direct sensing of NADPH/NADP+ redox state in living cells. Spectrally tuning the Apollo-NADP+ sensor allows multiplex imaging for studies of oxidative stress in beta cells.

2023.4.24. 오현택

Dihydroxyacetone phosphate signals glucose availability to mTORC1 - Nature MetabolismLevels of the glycolytic intermediate metabolite dihydroxyacetone phosphate are shown to signal cellular glucose availability to the mTORC1 complex through an AMPK-independent route.

2023.4.10. 최은지

Anti-inflammatory functions of the glucocorticoid receptor require DNA bindingAbstract. The glucocorticoid receptor is an important immunosuppressive drug target and metabolic regulator that acts as a ligand-gated transcription factor. Ge

2023.4.3. 최민지

NRF2 activation induces NADH-reductive stress, providing a metabolic vulnerability in lung cancerA subset of lung cancer cell lines is sensitive to activation of the transcription factor NRF2. The metabolic state of a cancer cell dictates sensitivity to NRF2, whose activation results in a NADH/NAD+ imbalance. As a result, the blockade of mitochondrial Complex I is a synthetic lethality in NRF2-activated lung cancers.

2023.3.20. 오현택

Page updated

Google Sites

Report abuse