SIRT7–SREBP1 restrains cancer cell metabolic reprogramming by upregulating IDH1

Su, Fengting; Tang, Xiaolong; Li, Guo; Koeberle, Andreas; Liu, Baohua

doi:10.1007/s42764-021-00031-4

Cited by 7 publications

(5 citation statements)

References 45 publications

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“…Conversely, TMZ slightly reduced U118MG tumor g significantly at day 23 (Figure 2C) or at day 18 (Figure S4B), but TMZ did not signifi affect U138MG tumor growth (Figures 2D and S4C). Indeed, both U118MG and U1 have been described as having a low [43,45,46] and unmethylated [43,44] MGMT p respectively, suggesting poor response to TMZ, consistent with our observations.…”

Section: Tmz Affected Gbm In Vivo Tumor Growth Differently In Subcuta...supporting

confidence: 92%

“…Here, we investigated the effect of TMZ and Fingolimod treatments in GBM in vitro and in vivo models. We used different GBM cell lines, i.e., IDH1wt and MGMT hypermethylated U87MG human cells [ 40 , 41 , 42 , 43 , 44 ], IDH1wt and low MGMT methylated U118MG human cells [ 43 , 45 , 46 ], IDH1wt and unmethylated MGMT U138MG human cells [ 43 , 44 ], and IDH1wt and MGMT hypermethylated GL261 mouse cells recapitulating human GBM features [ 16 , 47 , 48 , 49 , 50 ]. Using in vitro 2D and 3D culture models, we demonstrated that TMZ displayed cytotoxic effects on the four GBM cells tested.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Temozolomide and Fingolimod Treatments in Glioblastoma Preclinical Models

Davy,

Genest,

Legrand

et al. 2023

Cancers

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Glioblastomas are malignant brain tumors which remain lethal due to their aggressive and invasive nature. The standard treatment combines surgical resection, radiotherapy, and chemotherapy using Temozolomide, albeit with a minor impact on patient prognosis (15 months median survival). New therapies evaluated in preclinical translational models are therefore still required to improve patient survival and quality of life. In this preclinical study, we evaluated the effect of Temozolomide in different models of glioblastoma. We also aimed to investigate the efficacy of Fingolimod, an immunomodulatory drug for multiple sclerosis also described as an inhibitor of the sphingosine-1-phosphate (S1P)/S1P receptor axis. The effects of Fingolimod and Temozolomide were analyzed with in vitro 2D and 3D cellular assay and in vivo models using mouse and human glioblastoma cells implanted in immunocompetent or immunodeficient mice, respectively. We demonstrated both in in vitro and in vivo models that Temozolomide has a varied effect depending on the tumor type (i.e., U87MG, U118MG, U138MG, and GL261), demonstrating sensitivity, acquired resistance, and purely resistant tumor phenotypes, as observed in patients. Conversely, Fingolimod only reduced in vitro 2D tumor cell growth and increased cytotoxicity. Indeed, Fingolimod had little or no effect on 3D spheroid cytotoxicity and was devoid of effect on in vivo tumor progression in Temozolomide-sensitive models. These results suggest that the efficacy of Fingolimod is dependent on the glioblastoma tumor microenvironment. Globally, our data suggest that the response to Temozolomide varies depending on the cancer model, consistent with its clinical activity, whereas the potential activity of Fingolimod may merit further evaluation.

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Section: Tmz Affected Gbm In Vivo Tumor Growth Differently In Subcuta...supporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Evaluation of Temozolomide and Fingolimod Treatments in Glioblastoma Preclinical Models

Davy,

Genest,

Legrand

et al. 2023

Cancers

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“…Moreover, in breast carcinoma, SIRT6 acts as a tumor suppressor [ 85 ], which is correlated with an increased H3K9ac mark resulting in enhanced expression of glycolytic genes [ 86 ]. SIRT7 promotes isocitrate dehydrogenase 1 (IDH1) transcription in a SERPINE1 mRNA binding protein 1 (SERBP1) dependent manner to increase the α-keto-glutarate level and thereby enhance gluconeogenesis and lipogenesis, and destabilize HIF1α, to reverses glycolysis [ 87 ]. Basically, this SIRT7–IDH1 axis works to regulate metabolic reprogramming in cancer cells and, hence can help with therapeutic interventions [ 87 ].…”

Section: Epigenetic Reprogramming Of Metabolic Pathways – a Root Caus...mentioning

confidence: 99%

“…SIRT7 promotes isocitrate dehydrogenase 1 (IDH1) transcription in a SERPINE1 mRNA binding protein 1 (SERBP1) dependent manner to increase the α-keto-glutarate level and thereby enhance gluconeogenesis and lipogenesis, and destabilize HIF1α, to reverses glycolysis [ 87 ]. Basically, this SIRT7–IDH1 axis works to regulate metabolic reprogramming in cancer cells and, hence can help with therapeutic interventions [ 87 ]. Apart from epigenetic enzymes, the roles of different chromatin readers, which regulate metabolic programs, have been investigated.…”

Section: Epigenetic Reprogramming Of Metabolic Pathways – a Root Caus...mentioning

confidence: 99%

A prismatic view of the epigenetic-metabolic regulatory axis in breast cancer therapy resistance

Das,

Bhattacharya,

Adhikari

et al. 2024

Oncogene

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Epigenetic regulation established during development to maintain patterns of transcriptional expression and silencing for metabolism and other fundamental cell processes can be reprogrammed in cancer, providing a molecular mechanism for persistent alterations in phenotype. Metabolic deregulation and reprogramming are thus an emerging hallmark of cancer with opportunities for molecular classification as a critical preliminary step for precision therapeutic intervention. Yet, acquisition of therapy resistance against most conventional treatment regimens coupled with tumor relapse, continue to pose unsolved problems for precision healthcare, as exemplified in breast cancer where existing data informs both cancer genotype and phenotype. Furthermore, epigenetic reprograming of the metabolic milieu of cancer cells is among the most crucial determinants of therapeutic resistance and cancer relapse. Importantly, subtype-specific epigenetic-metabolic interplay profoundly affects malignant transformation, resistance to chemotherapy, and response to targeted therapies. In this review, we therefore prismatically dissect interconnected epigenetic and metabolic regulatory pathways and then integrate them into an observable cancer metabolism-therapy-resistance axis that may inform clinical intervention. Optimally coupling genome-wide analysis with an understanding of metabolic elements, epigenetic reprogramming, and their integration by metabolic profiling may decode missing molecular mechanisms at the level of individual tumors. The proposed approach of linking metabolic biochemistry back to genotype, epigenetics, and phenotype for specific tumors and their microenvironment may thus enable successful mechanistic targeting of epigenetic modifiers and oncometabolites despite tumor metabolic heterogeneity.

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“…Further research studies have shown that SIRT7 enhances IDH1 transcription, and that SIRT7 insufficiency downregulates IDH1 expression, resulting in cell metabolic reprogramming during tumorigenesis [ 167 ]. IDH1 mRNA and protein levels were found elevated in primary GB supporting the aggressive tumor growth and therapy resistance, while IDH1 inactivation promoted apoptosis and enhanced response to targeted therapies [ 168 ].…”

Section: Evidence Of Sirts Implication In Gb Pathogenesismentioning

confidence: 99%

Exploring the Multi-Faceted Role of Sirtuins in Glioblastoma Pathogenesis and Targeting Options

Kunadis

Piperi

2022

IJMS

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Recent advances in glioblastoma (GB) research have shed light on the molecular characteristics, the defected intracellular signaling pathways, and the genetic and epigenetic alterations involved in their pathogenesis. Despite constant efforts, GB remains an aggressive malignant tumor with limited therapeutic approaches, poor prognosis, and a low survival rate. Emerging evidence points towards the crucial impact of epigenetic post-translational modifications in cancer development with emphasis on the regulatory role of histone deacetylation in several key cellular processes, including metabolic pathways, regulation of stress response, senescence, proliferation, DNA repair, and apoptosis. The silent information regulator proteins (Sirtuins) are deacetylases of histone and non-histone proteins that have been recently implicated in the initiation as well as in the progression of GB. Herein, we provide a critical overview of the emerging functional role and mechanism of action of the seven Sirtuins (SIRT1-7) in GB and discuss their potential targeting options in clinical practice.

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SIRT7–SREBP1 restrains cancer cell metabolic reprogramming by upregulating IDH1

Cited by 7 publications

References 45 publications

Evaluation of Temozolomide and Fingolimod Treatments in Glioblastoma Preclinical Models

Evaluation of Temozolomide and Fingolimod Treatments in Glioblastoma Preclinical Models

A prismatic view of the epigenetic-metabolic regulatory axis in breast cancer therapy resistance

Exploring the Multi-Faceted Role of Sirtuins in Glioblastoma Pathogenesis and Targeting Options

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