Autophagy and Tumor Metabolism

Kimmelman, Alec C.; White, Eileen

doi:10.1016/j.cmet.2017.04.004

Cited by 679 publications

(598 citation statements)

References 79 publications

(95 reference statements)

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“…The TME is the cellular environment in which the tumor exists, including surrounding blood vessels, immune cells, fibroblasts, bone-marrow-derived inflammatory cells, lymphocytes, signaling molecules and the extracellular matrix [6,7]. Metabolites and recently highlighted factors regulating tumor-TME cell interaction are important elements in the TME [1,8].…”

Section: Original Papermentioning

confidence: 99%

Increased Lactate in Gastric Cancer Tumor-Infiltrating Lymphocytes Is Related to Impaired T Cell Function Due to miR-34a Deregulated Lactate Dehydrogenase A

Wang

Senyan

et al. 2018

Cell Physiol Biochem

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Background/Aims: Lactate is one of the products of glycolysis and is a hallmark of the Warburg effect. Glycolysis is found in tumor as well as immune cells. However, the effects of lactate on the function of tumor-infiltrating T cells (TILs) are rarely reported. Methods: In the present study, we investigated lactate and other glycolysis-related metabolites within TILs of human gastric cancer (GC). Lactate concentration was determined by liquid chromatography–mass spectrometry. The functional effects and clinical relevance of excessive lactate on T cells were investigated in clinical samples, and the mechanism of increased lactate was explored. Results: Lactate was significantly increased in GC TILs and related to decreased T helper (Th)1 cells and cytotoxic T lymphocytes (CTLs). Increased lactate within GC TILs was positively correlated with increased lactate dehydrogenase A (LDH)A. Expression of LDHA in GC TILs was also negatively correlated with percentages of Th1 cells and CTLs. Decreased miR-34a expression in GC TILs was responsible for increased expression of LDHA. A hypoxic tumor environment was responsible for decreased miR-34a and lactate-induced impaired immune function. Conclusion: We found that hypoxia decreases miR-34a expression and lose miR-34a regulation on LDHA, thus increasing lactate level within GC TILs and impairing immune function in GC.

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Section: Original Papermentioning

confidence: 99%

Increased Lactate in Gastric Cancer Tumor-Infiltrating Lymphocytes Is Related to Impaired T Cell Function Due to miR-34a Deregulated Lactate Dehydrogenase A

Wang

Senyan

et al. 2018

Cell Physiol Biochem

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“…Autophagy plays a complicated role in cell growth, development and tumorigenesis (Guo, Xia, & White, ), inhibiting cancer cells growth or promoting tumor cells survival (Kimmelman & White, ; White & DiPaola, ). A lot of anticancer agents display antitumor activity via affecting autophagy of cancer cells (Nagelkerke, Bussink, Geurts‐Moespot, Sweep, & Span, ; Yoshida, ; Zarzynska, ).…”

Section: Discussionmentioning

confidence: 99%

Maslinic acid induces autophagy by down‐regulating HSPA8 in pancreatic cancer cells

Tian

Farooq

et al. 2018

Phytotherapy Research

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Maslinic acid (MA), a natural pentacyclictriterpene, displays cytotoxic activity on various types of cancer cells. However, its underlying mechanism is unclear. In this study, we assessed the effect of MA on autophagy of human pancreatic cancer cells, and the potential autophagic pathway was presented. MA inhibited the proliferation and induced autophagy of Panc-28 cells by altering the expressions of autophagy related proteins. SDS-PAGE analysis revealed that one protein band was significantly down-regulated in cells treated with MA, and the band was identified as heat shock protein HSPA8 as analyzed using Western blot and MS, MS/MS approaches. HSPA8 knockdown could significantly inhibit cell viability and enhance the cytotoxic effects of MA, whereas HSPA8 overexpression was able to enhance cell viability, diminishing the effects of MA. Western blot analysis indicated that the effect of MA on the expression of autophagy related genes was increased significantly in cells treated with HSPA8 inhibitor VER-155008, whereas HSPA8 inducer geranylgeranylacetone antagonized the effects of MA. Our study provides evidence that MA is able to induce of autophagy via down-regulation of HSPA8 in Panc-28 cells.

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“…Macroautophagy (hereafter autophagy) is a complex intracellular process that can result in self-digestion of intracellular material to restore homeostasis in response to starvation or stress (Mizushima et al 2011; Kimmelman & White 2017). As noted above, autophagic flux may vary between cells in a population, contributing to variability in cell death sensitivity upon oncogene ablation (Viale et al 2014).…”

Section: Molecular Processes Implicated In the Generation Of Cellularmentioning

confidence: 99%

The impact of non-genetic heterogeneity on cancer cell death

Inde

Dixon

2017

Critical Reviews in Biochemistry and Molecular Biology

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The goal of chemotherapy is to induce homogeneous cell death within the population of targeted cancer cells. However, no two cells are exactly alike at the molecular level, and sensitivity to drug-induced cell death therefore varies within a population. Genetic alterations can contribute to this variability and lead to selection for drug resistant clones. However, there is a growing appreciation for the role of non-genetic variation in producing drug tolerant cellular states that exhibit reduced sensitivity to cell death for extended periods of time, from hours to weeks. These cellular states may result from individual variation in epigenetics, gene expression, metabolism and other processes that impact drug mechanism of action or the execution of cell death. Such population-level non-genetic heterogeneity may contribute to treatment failure and provide a cellular ‘substrate’ for the emergence of genetic alterations that confer frank drug resistance.

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Autophagy and Tumor Metabolism

Cited by 679 publications

References 79 publications

Increased Lactate in Gastric Cancer Tumor-Infiltrating Lymphocytes Is Related to Impaired T Cell Function Due to miR-34a Deregulated Lactate Dehydrogenase A

Increased Lactate in Gastric Cancer Tumor-Infiltrating Lymphocytes Is Related to Impaired T Cell Function Due to miR-34a Deregulated Lactate Dehydrogenase A

Maslinic acid induces autophagy by down‐regulating HSPA8 in pancreatic cancer cells

The impact of non-genetic heterogeneity on cancer cell death

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