Regulation of cancer cell metabolism

Nature reviews. Cancer, Journal Year: 2011, Volume and Issue: 11(2), P. 85 - 95

Published: Jan. 24, 2011

Language: Английский

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AMPK: guardian of metabolism and mitochondrial homeostasis

Nature Reviews Molecular Cell Biology, Journal Year: 2017, Volume and Issue: 19(2), P. 121 - 135

Published: Oct. 4, 2017

Language: Английский

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The AMPK signalling pathway coordinates cell growth, autophagy and metabolism

Nature Cell Biology, Journal Year: 2011, Volume and Issue: 13(9), P. 1016 - 1023

Published: Sept. 1, 2011

Language: Английский

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Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy

Science, Journal Year: 2010, Volume and Issue: 331(6016), P. 456 - 461

Published: Dec. 24, 2010

Adenosine monophosphate-activated protein kinase (AMPK) is a conserved sensor of intracellular energy activated in response to low nutrient availability and environmental stress. In screen for substrates AMPK, we identified ULK1 ULK2, mammalian orthologs the yeast Atg1, which required autophagy. Genetic analysis AMPK or liver Caenorhabditis elegans revealed requirement these kinases mammals, loss resulted aberrant accumulation autophagy adaptor p62 defective mitophagy. Reconstitution ULK1-deficient cells with mutant that cannot be phosphorylated by such phosphorylation mitochondrial homeostasis cell survival during starvation. These findings uncover biochemical mechanism coupling status survival.

Language: Английский

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Autophagy and Metabolism

Science, Journal Year: 2010, Volume and Issue: 330(6009), P. 1344 - 1348

Published: Dec. 2, 2010

Autophagy is a process of self-cannibalization. Cells capture their own cytoplasm and organelles consume them in lysosomes. The resulting breakdown products are inputs to cellular metabolism, through which they used generate energy build new proteins membranes. preserves the health cells tissues by replacing outdated damaged components with fresh ones. In starvation, it provides an internal source nutrients for generation and, thus, survival. A powerful promoter metabolic homeostasis at both whole-animal level, autophagy prevents degenerative diseases. It does have downside, however--cancer exploit survive nutrient-poor tumors.

Language: Английский

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Serine, glycine and one-carbon units: cancer metabolism in full circle

Nature reviews. Cancer, Journal Year: 2013, Volume and Issue: 13(8), P. 572 - 583

Published: July 4, 2013

Language: Английский

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STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS-Mutant Lung Adenocarcinoma

Cancer Discovery, Journal Year: 2018, Volume and Issue: 8(7), P. 822 - 835

Published: May 17, 2018

Abstract KRAS is the most common oncogenic driver in lung adenocarcinoma (LUAC). We previously reported that STK11/LKB1 (KL) or TP53 (KP) comutations define distinct subgroups of KRAS-mutant LUAC. Here, we examine efficacy PD-1 inhibitors these subgroups. Objective response rates to blockade differed significantly among KL (7.4%), KP (35.7%), and K-only (28.6%) (P < 0.001) Stand Up To Cancer (SU2C) cohort (174 patients) with LUAC patients treated nivolumab CheckMate-057 phase III trial (0% vs. 57.1% 18.2%; P = 0.047). In SU2C cohort, exhibited shorter progression-free overall 0.0015) survival compared KRASMUT;STK11/LKB1WT Among 924 LUACs, alterations were only marker associated PD-L1 negativity TMBIntermediate/High The impact on clinical outcomes PD-1/PD-L1 extended PD-L1–positive non–small cell cancer. Kras-mutant murine models, Stk11/Lkb1 loss promoted inhibitor resistance, suggesting a causal role. Our results identify as major primary resistance Significance: This work identifies prevalent genomic axis adenocarcinoma. Genomic profiling may enhance predictive utility expression tumor mutation burden facilitate establishment personalized combination immunotherapy approaches for genomically defined subsets. Discov; 8(7); 822–35. ©2018 AACR. See related commentary by Etxeberria et al., p. 794. article highlighted Issue feature, 781

Language: Английский

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Metabolic pathways promoting cancer cell survival and growth

Nature Cell Biology, Journal Year: 2015, Volume and Issue: 17(4), P. 351 - 359

Published: March 16, 2015

Language: Английский

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Autophagy-Dependent Anticancer Immune Responses Induced by Chemotherapeutic Agents in Mice

Science, Journal Year: 2011, Volume and Issue: 334(6062), P. 1573 - 1577

Published: Dec. 15, 2011

Antineoplastic chemotherapies are particularly efficient when they elicit immunogenic cell death, thus provoking an anticancer immune response. Here we demonstrate that autophagy, which is often disabled in cancer, dispensable for chemotherapy-induced death but required its immunogenicity. In response to chemotherapy, autophagy-competent, not autophagy-deficient, cancers attracted dendritic cells and T lymphocytes into the tumor bed. Suppression of autophagy inhibited release adenosine triphosphate (ATP) from dying cells. Conversely, inhibition extracellular ATP-degrading enzymes increased pericellular ATP autophagy-deficient tumors, reestablished recruitment cells, restored chemotherapeutic responses only immunocompetent hosts. Thus, essential concentrations improve efficacy antineoplastic disabled.

Language: Английский

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Fueling Immunity: Insights into Metabolism and Lymphocyte Function

Science, Journal Year: 2013, Volume and Issue: 342(6155)

Published: Oct. 10, 2013

Lymphocytes face major metabolic challenges upon activation. They must meet the bioenergetic and biosynthetic demands of increased cell proliferation also adapt to changing environmental conditions, in which nutrients oxygen may be limiting. An emerging theme immunology is that reprogramming lymphocyte activation are intricately linked. However, why T cells adopt specific programs impact these have on function and, ultimately, immunological outcome remain unclear. Research tumor metabolism has provided valuable insight into pathways important for influence metabolites themselves signal transduction epigenetic programming. In this Review, we highlight concepts regarding proliferating discuss their potential fate function.

Language: Английский

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