Sirtuins' control of autophagy and mitophagy in cancer

Aventaggiato, Michele; Vernucci, Enza; Barreca, Federica; Russo, Matteo Antonio; Tafani, Marco

doi:10.1016/j.pharmthera.2020.107748

Cited by 78 publications

(65 citation statements)

References 521 publications

(519 reference statements)

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“…Mitochondria are the main oxygen consumers at the crossroads of apoptotic pathways induced by anticancer agents, and excess mitochondrial activity leads to local hypoxia in the tumor microenvironment ( Figure 3 ) ( 112 , 113 ). Hypoxia may promote mitophagy, thereby mediating resistance to cisplatin ( 114 ), while mitophagy during hypoxia may limit ROS production ( 115 , 116 ). Hypoxic cells in NSCLC are also more resistant to chemotherapeutics and radiation.…”

Section: Pgc-1α/ppar-γ Signaling In Hypoxia-induced Chemoresistance In Nsclcmentioning

confidence: 99%

SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer

Luo

et al. 2021

Front. Oncol.

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Resistance is the major cause of treatment failure and disease progression in non-small cell lung cancer (NSCLC). There is evidence that hypoxia is a key microenvironmental stress associated with resistance to cisplatin, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), and immunotherapy in solid NSCLCs. Numerous studies have contributed to delineating the mechanisms underlying drug resistance in NSCLC; nevertheless, the mechanisms involved in the resistance associated with hypoxia-induced molecular metabolic adaptations in the microenvironment of NSCLC remain unclear. Studies have highlighted the importance of posttranslational regulation of molecular mediators in the control of mitochondrial function in response to hypoxia-induced metabolic adaptations. Hypoxia can upregulate the expression of sirtuin 1 (SIRT1) in a hypoxia-inducible factor (HIF)-dependent manner. SIRT1 is a stress-dependent metabolic sensor that can deacetylate some key transcriptional factors in both metabolism dependent and independent metabolic pathways such as HIF-1α, peroxisome proliferator-activated receptor gamma (PPAR-γ), and PPAR-gamma coactivator 1-alpha (PGC-1α) to affect mitochondrial function and biogenesis, which has a role in hypoxia-induced chemoresistance in NSCLC. Moreover, SIRT1 and HIF-1α can regulate both innate and adaptive immune responses through metabolism-dependent and -independent ways. The objective of this review is to delineate a possible SIRT1/PGC-1α/PPAR-γ signaling-related molecular metabolic mechanism underlying hypoxia-induced chemotherapy resistance in the NSCLC microenvironment. Targeting hypoxia-related metabolic adaptation may be an attractive therapeutic strategy for overcoming chemoresistance in NSCLC.

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Section: Pgc-1α/ppar-γ Signaling In Hypoxia-induced Chemoresistance In Nsclcmentioning

confidence: 99%

SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer

Luo

et al. 2021

Front. Oncol.

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“…Class I and II HDACs were found to show high similarities in catalytic sites. Except for HDAC8, HDAC isoforms appear to combine with more proteins or more HDAC isoforms in multiprotein complexes ( 13 , 14 ). Many types of HDACs are derived from nucleotide polymorphisms and optional splicing.…”

Section: Hdac Classificationsmentioning

confidence: 99%

Characterization of Histone Deacetylase Mechanisms in Cancer Development

Hai

Shu

et al. 2021

Front. Oncol.

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Over decades of studies, accumulating evidence has suggested that epigenetic dysregulation is a hallmark of tumours. Post-translational modifications of histones are involved in tumour pathogenesis and development mainly by influencing a broad range of physiological processes. Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are pivotal epigenetic modulators that regulate dynamic processes in the acetylation of histones at lysine residues, thereby influencing transcription of oncogenes and tumour suppressor genes. Moreover, HDACs mediate the deacetylation process of many nonhistone proteins and thus orchestrate a host of pathological processes, such as tumour pathogenesis. In this review, we elucidate the functions of HDACs in cancer.

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“…Environmental stress during Bone marrow mesenchymal stem cells (BMSCs) transplantation or in damaged tissues can lead to catastrophic problems, such as cytotoxicity and poor survival of BMSCs. Mitophagy plays an important role in promoting mitochondrial division of BMSCs [ 3 ]. Mitophagy promotes the stemness of bone marrow-derived mesenchymal stem cells by regulating mitochondrial fission, and inhibition of mitophagy suppresses the stemness of BMSCs [ 42 ].…”

Section: Effects Of Mitophagy On Mesenchymal Stem Cellsmentioning

confidence: 99%

“…Thus, the entire mitochondrial cycle, from biogenesis to death, either through mitophagy or through apoptosis, can be targeted by different drugs to reduce mitochondrial fitness and thus restore or increase sensitivity to chemotherapeutic drugs [ 68 ]. Mitochondrial biogenesis has become an important target for the study of anti-CSC drug resistance mechanisms due to the high mitochondrial content in CSCs [ 3 ]. The use of mitochondrial targeting therapy to target CSCs may be valuable, but there are challenges to mitochondrial targeting therapy [ 69 ].…”

Section: Effects Of Mitophagy On Cancer Stem Cellsmentioning

confidence: 99%

“…Mitochondria, as semiautonomous organelles, can participate in various cellular functions, including ATP production, oxidative stress and calcium signal transduction [ 2 ]. If a cell undergoes a process such as proliferation or differentiation in the presence of inadequately functional mitochondria, it is likely to undergo a metabolic crisis [ 3 ], leading to cell death or senescence. Mitochondrial division and fusion are the mechanisms by which mitochondrial quality control can be evaluated.…”

Section: Introductionmentioning

confidence: 99%

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New insights into mitophagy and stem cells

Lin

Chen

et al. 2021

Stem Cell Res Ther

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Mitophagy is a specific autophagic phenomenon in which damaged or redundant mitochondria are selectively cleared by autophagic lysosomes. A decrease in mitophagy can accelerate the aging process. Mitophagy is related to health and longevity and is the key to protecting stem cells from metabolic stress damage. Mitophagy decreases the metabolic level of stem cells by clearing active mitochondria, so mitophagy is becoming increasingly necessary to maintain the regenerative capacity of old stem cells. Stem cell senescence is the core problem of tissue aging, and tissue aging occurs not only in stem cells but also in transport amplifying cell chambers and the stem cell environment. The loss of the autophagic ability of stem cells can cause the accumulation of mitochondria and the activation of the metabolic state as well as damage the self-renewal ability and regeneration potential of stem cells. However, the claim remains controversial. Mitophagy is an important survival strategy against nutrient deficiency and starvation, and mitochondrial function and integrity may affect the viability, proliferation and differentiation potential, and longevity of normal stem cells. Mitophagy can affect the health and longevity of the human body, so the number of studies in this field has increased, but the mechanism by which mitophagy participates in stem cell development is still not fully understood. This review describes the potential significance of mitophagy in stem cell developmental processes, such as self-renewal, differentiation and aging. Through this work, we discovered the role and mechanism of mitophagy in different types of stem cells, identified novel targets for killing cancer stem cells and curing cancer, and provided new insights for future research in this field.

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Sirtuins' control of autophagy and mitophagy in cancer

Cited by 78 publications

References 521 publications

SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer

SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer

Characterization of Histone Deacetylase Mechanisms in Cancer Development

New insights into mitophagy and stem cells

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