SIRT3 inhibits gallbladder cancer by induction of AKT-dependent ferroptosis and blockade of epithelial-mesenchymal transition

Liu, Liguo; Yang, Li; Cao, Dongyan; Qiu, Shimei; Li, Yongsheng; Jiang, Chengkai; Bian, Rui; Yang, Yang; Li, Lin; Li, Xuechuan; Wang, Ziyi; Zheng, Jian; Zhang, Yijian; Liu, Yingbin

doi:10.1016/j.canlet.2021.04.007

Cited by 62 publications

(53 citation statements)

References 31 publications

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“…SIRT3 plays a significant inhibitory role in the cancer metastasis process. SIRT3 regulates the EMT-related markers such as E-Cadherin, N-Cadherin, and Vimentin to suppress EMT, especially in prostate cancer and small-cell lung cancer, which may be related to Wnt/b-catenin/FOXO3a pathway and protein kinase B (AKT, also known as PKB)-dependent ferroptosis (79)(80)(81). In ovarian cancer, as a key regulator of EMT, Twist is down-regulated by SIRT3 to suppress the metastasis of the tumor (82).…”

Section: Regulation Of Cancer Metastasis By Sirt3mentioning

confidence: 99%

The Role and Therapeutic Perspectives of Sirtuin 3 in Cancer Metabolism Reprogramming, Metastasis, and Chemoresistance

Zhao

Zhou

et al. 2022

Front. Oncol.

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Sirtuin 3 (SIRT3), the nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, acts as a metabolic modulator mainly located in mitochondria via regulating the process of the relevant biochemical processes by targeting crucial mediators. Recently, owing to its dual role in cancer, SIRT3 has attracted extensive attention. Cancer cells have different metabolic patterns from normal cells, and SIRT3-mediated metabolism reprogramming could be critical in the cancer context, which is closely related to the mechanism of metabolism reprogramming, metastasis, and chemoresistance in tumor cells. Therefore, it is crucial to elucidate the relevant pathological mechanisms and take appropriate countermeasures for the progression of clinical strategies to inhibit the development of cancer. In this review, existing available data on the regulation of cancer metabolism reprogramming, metastasis, and chemoresistance progression of SIRT3 are detailed, as well as the status quo of SIRT3 small molecule modulators is updated in the application of cancer therapy, aiming to highlight strategies directly targeting SIRT3-mediated tumor-suppressing and tumor-promoting, and provide new approaches for therapy application. Furthermore, we offer an effective evidence-based basis for the evolvement of potential personalized therapy management strategies for SIRT3 in cancer settings.

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Section: Regulation Of Cancer Metastasis By Sirt3mentioning

confidence: 99%

The Role and Therapeutic Perspectives of Sirtuin 3 in Cancer Metabolism Reprogramming, Metastasis, and Chemoresistance

Zhao

Zhou

et al. 2022

Front. Oncol.

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“…Both SIRT2 and SIRT3 can inhibit ferroptosis through downregulating p53 [ 52 , 53 ]. Moreover, SIRT3 can also inhibit AKT-dependent mitochondrial metabolism and promoting AMPK-mTOR pathway and decreasing GPX4 level to induce ferroptosis [ 54 , 55 ]. SIRT6 inhibition can lead to the inactivation of the Keap1/Nrf2 signaling pathway and downregulation of GPX4, which in turn triggers ferroptosis [ 56 ].…”

Section: An Adiposity-based Chronic Disease (Abcd)mentioning

confidence: 99%

Research Progress of Ferroptosis in Adiposity-Based Chronic Disease (ABCD)

Ren

Bai

et al. 2022

Oxidative Medicine and Cellular Longevity

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Ferroptosis is a multistep regulated cell death process induced by iron accumulation and lipid peroxidation. Classical GPX4-dependent pathway and GPX4-independent pathways can independently and synergistically inhibit ferroptosis and jointly maintain the oxidative balance of the body. WHO defines obesity as “a condition of abnormal or excessive fat accumulation in adipose tissue, to the extent that health may be impaired,” and obesity is also defined as an adiposity-based chronic disease (ABCD). Obesity is a systemic disease that leads to metabolic abnormalities in various systems, resulting in a series of complications including obesity cardiomyopathy, atherosclerosis, nonalcoholic fatty liver disease, and diabetes mellitus. Emerging evidence shows that ferroptosis is closely associated with the occurrence and progression of various diseases. In recent years, ferroptosis has been found to play critical roles in obesity and its complications. This review discusses the mechanisms of how ferroptosis is initiated and controlled and discusses the research progress of ferroptosis in obesity and its complications.

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“…SIRT3 is reportedly involved in the induction of autophagy‐dependent ferroptosis via the activation of the activated protein kinase–mTOR pathway and GPX4 suppression, indicating that SIRT3 deficiency provides resistance against the inductions of high‐glucose–induced autophagy and its resulting ferroptosis 30 . Interestingly, a study on gallbladder cancer indicated that SIRT3 plays a role in the inhibition of AKT serine/threonine kinase 1–dependent mitochondrial metabolism, as well as in the blockade of epithelial‐mesenchymal transition, which thus can lead to tumor suppression by ferroptosis 31 . On the contrary, a study on traumatic brain injury indicated that SIRT2 can exert a suppressive function against TP53‐mediated ferroptosis 32 .…”

Section: Sirtuins Regulate Ferroptosis In Damaged Cellsmentioning

confidence: 99%

“… 30 Interestingly, a study on gallbladder cancer indicated that SIRT3 plays a role in the inhibition of AKT serine/threonine kinase 1–dependent mitochondrial metabolism, as well as in the blockade of epithelial‐mesenchymal transition, which thus can lead to tumor suppression by ferroptosis. 31 On the contrary, a study on traumatic brain injury indicated that SIRT2 can exert a suppressive function against TP53‐mediated ferroptosis. 32 A study using an experimental traumatic brain injury model suggests that the deacetylase function of SIRT2 is associated with the deacetylation of TP53, which inhibits TP53 expression and thus suppresses TP53‐mediated ferroptosis.…”

Section: Sirtuins Regulate Ferroptosis In Damaged Cellsmentioning

confidence: 99%

Cancer metabolism challenges genomic instability and clonal evolution as therapeutic targets

et al. 2022

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Although cancer precision medicine has improved diagnosis and therapy, refractory cancers such as pancreatic cancer remain to be challenging targets. Clinical sequencing has identified the significant alterations in driver genes and traced their clonal evolutions. Recent studies indicated that the tumor microenvironment elicits altera-How to cite this article: Takeda Y, Chijimatsu R, Ofusa K, et al. Cancer metabolism challenges genomic instability and clonal evolution as therapeutic targets.

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SIRT3 inhibits gallbladder cancer by induction of AKT-dependent ferroptosis and blockade of epithelial-mesenchymal transition

Cited by 62 publications

References 31 publications

The Role and Therapeutic Perspectives of Sirtuin 3 in Cancer Metabolism Reprogramming, Metastasis, and Chemoresistance

The Role and Therapeutic Perspectives of Sirtuin 3 in Cancer Metabolism Reprogramming, Metastasis, and Chemoresistance

Research Progress of Ferroptosis in Adiposity-Based Chronic Disease (ABCD)

Cancer metabolism challenges genomic instability and clonal evolution as therapeutic targets

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