Sirt1 induction confers resistance to etoposide-induced genotoxic apoptosis in thyroid cancers

Kweon, Ki Hwan; Lee, Cho Rok; Jung, Soo Jung; Ban, Eun Jeong; Kang, Sang–Wook; Jeong, Jong Ju; Nam, Kee Hyun; Jo, Young Suk; Lee, Jandee; Chung, Woong Youn

doi:10.3892/ijo.2014.2585

Cited by 17 publications

(13 citation statements)

References 48 publications

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“…31,32) Previous reports using trans- the heterogeneous expression of SIRT1 between tumor tissues and normal tissues. 9) We also observed the expression patterns in normal thyroid lesions and thyroid tumor tissues; however, SIRT1 expression was very heterogeneous, and we did not find significant changes between normal tissues and tumor tissues.…”

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confidence: 48%

Prognostic Significance of Sirtuins Expression in Papillary Thyroid Carcinoma

et al. 2018

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Background and Objectives: Sirtuins (SIRTs) play important roles in cellular and organismal homeostasis. They have distinct gene expression patterns in various cancers; however, the relationship between SIRT expression and the progression of thyroid cancer is unclear. We investigated the expression of SIRTs in patients with papillary thyroid carcinoma (PTC) and their role as biomarkers for predicting the aggressiveness of this disease. Materials and Methods: We used immunohistochemical staining to evaluate the expression of SIRT1 and SIRT3 in tumor specimens from 270 patients with PTC. We also evaluated the potential association between SIRT expression and diverse clinicopathological features. Results: High SIRT1 expression was negatively correlated with lymphovascular invasion, central lymph node metastasis, and lateral lymph node metastasis. Multivariate analyses revealed that high SIRT1 expression was a negative independent risk factor for lateral lymph node metastasis. By contrast, high SIRT3 expression was positively correlated with locoregional recurrence. Interestingly, when patients were grouped by tumor SIRT expression patterns, the group with low SIRT1 expression and high SIRT3 expression was correlated with more aggressive cancer phenotypes including central lymph node metastasis and lateral lymph node metastasis. Conclusion: Our results suggest that SIRTs play dual roles in tumor progression, and the combination of decreased SIRT1 expression and increased SIRT3 expression is significantly associated with a poor prognosis in patients with PTC.

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Section: )supporting

confidence: 48%

Prognostic Significance of Sirtuins Expression in Papillary Thyroid Carcinoma

et al. 2018

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“…As shown in Figure 5a, treatment of MIN6 cells with cisplatin 35 or doxorubicin 36 increased TM7SF3 mRNA levels, suggesting that it could be upregulated also under certain types of genotoxic stress. Interestingly, thapsigargin, tunicamycin, cytokines and etoposide, 37 failed to increase or even slightly decreased the mRNA levels of TM7SF3 (Figure 5a), indicating that only a selected set of stress inducers affect TM7SF3 expression. Of note, a number of the agents that promoted expression of TM7SF3, also increased transcription of p21 ( Figure 5b), a known downstream target of p53.…”

Section: Resultsmentioning

confidence: 99%

TM7SF3, a novel p53-regulated homeostatic factor, attenuates cellular stress and the subsequent induction of the unfolded protein response

et al. 2016

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Earlier reported small interfering RNA (siRNA) high-throughput screens, identified seven-transmembrane superfamily member 3 (TM7SF3) as a novel inhibitor of pancreatic β-cell death. Here we show that TM7SF3 maintains protein homeostasis and promotes cell survival through attenuation of ER stress. Overexpression of TM7SF3 inhibits caspase 3/7 activation. In contrast, siRNA-mediated silencing of TM7SF3 accelerates ER stress and activation of the unfolded protein response (UPR). This involves inhibitory phosphorylation of eukaryotic translation initiation factor 2α activity and increased expression of activating transcription factor-3 (ATF3), ATF4 and C/EBP homologous protein, followed by induction of apoptosis. This process is observed both in human pancreatic islets and in a number of cell lines. Some of the effects of TM7SF3 silencing are evident both under basal conditions, in otherwise untreated cells, as well as under different stress conditions induced by thapsigargin, tunicamycin or a mixture of pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin-1 beta and interferon gamma). Notably, TM7SF3 is a downstream target of p53: activation of p53 by Nutlin increases TM7SF3 expression in a time-dependent manner, although silencing of p53 abrogates this effect. Furthermore, p53 is found in physical association with the TM7SF3 promoter. Interestingly, silencing of TM7SF3 promotes p53 activity, suggesting the existence of a negative-feedback loop, whereby p53 promotes expression of TM7SF3 that acts to restrict p53 activity. Our findings implicate TM7SF3 as a novel p53-regulated pro-survival homeostatic factor that attenuates the development of cellular stress and the subsequent induction of the UPR.

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“…For example, SIRT3 over-expression has been implicated in kidney cancer growth inhibition and maintaining mitochondrial homeostasis, as well as modulating ROS production to sensitize biomolecules and cells to oxidative damage [64], whereas low SIRT3 level is associated with poor differentiation and unfavorable prognosis in primary hepatocellular carcinoma (HCC) [65]. Moreover, anti-cancer agent etoposide-induced genotoxic-mediated cancer cell apoptosis has been shown to correlate with both SIRT1 and SIRT3 over-expression [66].…”

Section: Hypoxia-inducible Factorsmentioning

confidence: 99%

Metabolic Heterogeneity of Cancer Cells: An Interplay between HIF-1, GLUTs, and AMPK

Moldogazieva

Mokhosoev

Terentiev

2020

Cancers

117

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It has been long recognized that cancer cells reprogram their metabolism under hypoxia conditions due to a shift from oxidative phosphorylation (OXPHOS) to glycolysis in order to meet elevated requirements in energy and nutrients for proliferation, migration, and survival. However, data accumulated over recent years has increasingly provided evidence that cancer cells can revert from glycolysis to OXPHOS and maintain both reprogrammed and oxidative metabolism, even in the same tumor. This phenomenon, denoted as cancer cell metabolic plasticity or hybrid metabolism, depends on a tumor micro-environment that is highly heterogeneous and influenced by an intensity of vasculature and blood flow, oxygen concentration, and nutrient and energy supply, and requires regulatory interplay between multiple oncogenes, transcription factors, growth factors, and reactive oxygen species (ROS), among others. Hypoxia-inducible factor-1 (HIF-1) and AMP-activated protein kinase (AMPK) represent key modulators of a switch between reprogrammed and oxidative metabolism. The present review focuses on cross-talks between HIF-1, glucose transporters (GLUTs), and AMPK with other regulatory proteins including oncogenes such as c-Myc, p53, and KRAS; growth factor-initiated protein kinase B (PKB)/Akt, phosphatidyl-3-kinase (PI3K), and mTOR signaling pathways; and tumor suppressors such as liver kinase B1 (LKB1) and TSC1 in controlling cancer cell metabolism. The multiple switches between metabolic pathways can underlie chemo-resistance to conventional anti-cancer therapy and should be taken into account in choosing molecular targets to discover novel anti-cancer drugs.

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Sirt1 induction confers resistance to etoposide-induced genotoxic apoptosis in thyroid cancers

Cited by 17 publications

References 48 publications

Prognostic Significance of Sirtuins Expression in Papillary Thyroid Carcinoma

Prognostic Significance of Sirtuins Expression in Papillary Thyroid Carcinoma

TM7SF3, a novel p53-regulated homeostatic factor, attenuates cellular stress and the subsequent induction of the unfolded protein response

Metabolic Heterogeneity of Cancer Cells: An Interplay between HIF-1, GLUTs, and AMPK

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