SIRT3 inhibits prostate cancer by destabilizing oncoprotein c-MYC through regulation of the PI3K/Akt pathway

Quan, Yizhou; Wang, Naitao; Chen, Qianqian; Xu, Jin; Cheng, Wei; Di, Meijuan; Xia, Weiliang; Gao, Wei‐Qiang

doi:10.18632/oncotarget.4764

Cited by 60 publications

(50 citation statements)

References 48 publications

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“…More recently, depletion of SIRT3 was shown to exert tumor-suppressive function by regulating iron metabolism in pancreatic cancer (48). Also, exogenous overexpression of SIRT3 was shown to suppress prostate cancer by decreasing ROS generation which inhibits Akt phosphorylation at Ser 473 leading to ubiquitin-mediated proteosomal c-MYC degradation (49). …”

Section: Mitochondrial Sirts and Their Molecular Targets: Relevance Tmentioning

confidence: 99%

Mitochondrial Sirtuins in Cancer: Emerging Roles and Therapeutic Potential

George

Ahmad

2016

Cancer Research

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The past few decades have witnessed a furious attention of scientific community towards identifying novel molecular factors and targets which could be exploited for drug development for cancer management. One such factor is the sirtuin (SIRT) family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases. The role of SIRTs in cancer is extremely complex, with dichotomous functions depending on cell contexts. Mammalian SIRTs (SIRT1–7), differ in their cellular localization and biological functions. Amongst these, SIRT -3, -4, and -5 are located in the mitochondria and are being carefully investigated. These mitochondrial SIRTs (mtSIRTs) regulate multiple cellular and physiological processes, including cell cycle, gene expression, cell viability, stress response, metabolism and energy homeostasis. Recent research suggests that mtSIRTs influence tumors by regulating the metabolic state of the cell. While the research on the role of mtSIRTs in cancer is still in its infancy, studies have suggested tumor suppressor as well as tumor promoter roles for them. This review is focused on discussing an up-to-date information about the roles and functional relevance of mtSIRTs (SIRT -3, -4, -5) in cancers. We have also provided a critical discussion and our perspective on their dual roles, as tumor promoter versus tumor suppressor, in cancer.

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Section: Mitochondrial Sirts and Their Molecular Targets: Relevance Tmentioning

confidence: 99%

Mitochondrial Sirtuins in Cancer: Emerging Roles and Therapeutic Potential

George

Ahmad

2016

Cancer Research

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“…The upregulated expression of PI3K/AKT pathway was involved in PCa progression. Moreover, phosphorylated AKT (p‐AKT) was reported to target and stimulate the expression of tumorigenic factors like c‐myc and eventually robust tumor growth . In the study, we performed western blot for PI3K, AKT, phosphorylated PI3K (p‐PI3K), and p‐AKT in stable PCa cells.…”

Section: Resultsmentioning

confidence: 99%

“…The PI3K/AKT signal pathway had pivotal roles in cell survival, and upregulated activity of the PI3K/AKT pathway was involved in PCa progression . AKT phosphorylation was reported to target and stimulate the expression of tumorigenic factors like c‐Myc, thus robusting tumor growth. Inhibition of PI3K‐AKT signaling was found to result in Thr58 phosphorylation of c‐Myc, which led to the degradation of c‐Myc .…”

Section: Discussionmentioning

confidence: 99%

PSCA promotes prostate cancer proliferation and cell‐cycle progression by up‐regulating c‐Myc

Liu

et al. 2017

The Prostate

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“…Disorder of such pathway will result in multiple diseases, such as cancer genesis and progression, nervous system disease, autoimmune disease and hematopoietic system disease (13). …”

Section: Introductionmentioning

confidence: 99%

Anacardic acid induces cell apoptosis of prostatic cancer through autophagy by ER stress/DAPK3/Akt signaling pathway

et al. 2017

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Anacardic acid, which is commonly seen in plants of Anacardiaceae, is an important composition of cashew, ginkgo leaf and fruit, and it has been suggested in previous research to show antitumor activity. The main aim of the present study was to evaluate the anticancer effects of anacardic acid on cell apoptosis of prostatic cancer and molecular mechanisms of this phenomenon. In this study we found that anacardic acid inhibited cell proliferation, induced apoptosis and caspase-3/9 activities and Bax protein expression of prostatic cancer. Anacardic acid induced the ER stress inducing factors (BiP, CHOP, p-eIF2α), autophagy, LC3, Beclin-1, Atg 7 and DAPK3 protein expression, and suppressed p-Akt and p-mTOR protein expression of prostatic cancer. Si-CHOP was used to inhibit ER stress in prostatic cancer by anacardic acid, which showed that the cell proliferation was increased, apoptosis, and caspase-3/9 activities and Bax protein expression was suppressed, autophagy, LC3, Beclin-1, Atg 7 and DAPK3 protein expression was reduced, and p-Akt and p-mTOR protein expression was promoted. DAPK3 inhibited p-Akt and p-mTOR protein expression, enhanced the anticancer effects of anacardic acid on prostatic cancer through autophagy. For the first time, the present study showed that anacardic acid induces cell apoptosis of prostatic cancer through autophagy by ER stress/DAPK3/Akt signaling pathway.

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SIRT3 inhibits prostate cancer by destabilizing oncoprotein c-MYC through regulation of the PI3K/Akt pathway

Cited by 60 publications

References 48 publications

Mitochondrial Sirtuins in Cancer: Emerging Roles and Therapeutic Potential

Mitochondrial Sirtuins in Cancer: Emerging Roles and Therapeutic Potential

PSCA promotes prostate cancer proliferation and cell‐cycle progression by up‐regulating c‐Myc

Anacardic acid induces cell apoptosis of prostatic cancer through autophagy by ER stress/DAPK3/Akt signaling pathway

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