SIRT1 in Secretory Organ Cancer

Frazzi, Raffaele

doi:10.3389/fendo.2018.00569

Cited by 26 publications

(16 citation statements)

References 72 publications

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“…SIRT1 is ubiquitously expressed in the nucleus but shuttles between the nucleus and cytoplasm 4 . Similar to other HDACs, aberrant SIRT1 expression is reported in multiple human malignancies, namely, gastric, colon, prostate, and ovarian cancers, as well as breast cancer 5 - 11 . The implications of SIRT1 in breast cancer occurrence and progression have been investigated over recent years.…”

Section: Introductionmentioning

confidence: 79%

Loss of SIRT4 promotes the self-renewal of Breast Cancer Stem Cells

Li¹,

Liu²,

Ren³

et al. 2020

Theranostics

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Rationale: It has been proposed that cancer stem/progenitor cells (or tumor-initiating cells, TICs) account for breast cancer initiation and progression. Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent class-III histone deacetylases and mediate various basic biological processes, including metabolic homeostasis. However, interplay and cross-regulation among the sirtuin family are not fully understood. As one of the least studied sirtuin family members, the mitochondrial sirtuin SIRT4 is a tumor suppressor gene in various cancers. However, its role in cancer stemness, as well as initiation and progression of breast cancer, remains unknown. Methods: The expression of SIRT4 in breast cancer was analyzed using the TCGA breast cancer database and 3 GSEA data. Normal breast epithelial cells MCF10A and breast cancer cell lines MCF-7, MDA-MB-231, BT549, MDA-MB-468 were used to establish SIRT4 gene knockdown and corresponding overexpression cells. Identified MTT cytotoxicity assays, cell invasion and motility assay, sorting of SP, confocal immunofluorescence microscopy, mouse mammary stem cell analysis, glutamine and glucose production, clonogenic and sphere-formation assay, mass spectrometric metabolomics analysis and ChIP-seq to further explore SIRT4 biological role in breast cancer. Results: We elucidated a novel role for SIRT4 in the negative regulation of mammary gland development and stemness, which is related to the mammary tumorigenesis. We also uncovered an inverse correlation between SIRT4 and SIRT1. Most importantly, SIRT4 negatively regulates SIRT1 expression via repressing glutamine metabolism. Besides, we identified H4K16ac and BRCA1 as new prime targets of SIRT4 in breast cancer. Conclusions: These results demonstrate that SIRT4 exerts its tumor-suppressive activity via modulating SIRT1 expression in breast cancer and provide a novel cross-talk between mitochondrial and nuclear sirtuins.

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Section: Introductionmentioning

confidence: 79%

Loss of SIRT4 promotes the self-renewal of Breast Cancer Stem Cells

Li¹,

Liu²,

Ren³

et al. 2020

Theranostics

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“…As previously mentioned, NAM increases the levels of NAD + , boosts energy metabolism and protects cells from oxidative stress [39]. NAM also inhibits SIRT1 and PARP1, both of which have been shown to be up-regulated in multiple cancers [39,48,[137][138][139]. However, while it suppresses Despite the aforementioned evidence, more studies are needed to unravel NAM's entire molecular mechanism in diverse cancer scenarios, before its widespread implementation into clinical practice.…”

Section: Discussionmentioning

confidence: 99%

The Role of Nicotinamide in Cancer Chemoprevention and Therapy

2020

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Nicotinamide (NAM) is a water-soluble form of Vitamin B3 (niacin) and a precursor of nicotinamide-adenine dinucleotide (NAD+) which regulates cellular energy metabolism. Except for its role in the production of adenosine triphosphate (ATP), NAD+ acts as a substrate for several enzymes including sirtuin 1 (SIRT1) and poly ADP-ribose polymerase 1 (PARP1). Notably, NAM is an inhibitor of both SIRT1 and PARP1. Accumulating evidence suggests that NAM plays a role in cancer prevention and therapy. Phase III clinical trials have confirmed its clinical efficacy for non-melanoma skin cancer chemoprevention or as an adjunct to radiotherapy against head and neck, laryngeal, and urinary bladder cancers. Evidence for other cancers has mostly been collected through preclinical research and, in its majority, is not yet evidence-based. NAM has potential as a safe, well-tolerated, and cost-effective agent to be used in cancer chemoprevention and therapy. However, more preclinical studies and clinical trials are needed to fully unravel its value.

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“…In line with this, another study also reported that overexpression of SIRT1 in HCC cells is positively associated with micro vascular invasion and metastasis through the stimulation of PGC-1α-mediated mitochondrial biogenesis resulting in poor treatment outcome [55]. This was also supported by Frazzi, who showed that an overexpression of SIRT1 results in poor treatment outcome and short life expectancy in patients with HCC [56]. But be sure that the subcellular localization of SIRT1 can be varied from cell to cell, and some cells appeared to have nuclear expression of SIRT1 whereas others expressed it within the cytoplasm or in both [57].…”

Section: Role Of Sirt1 In Hepatocellular Carcinoma Progressionmentioning

confidence: 53%

Hepatocellular Expression of SIRT1 and Its Effect on Hepatocellular Carcinoma Progression: A Future Therapeutic Perspective

Molla

Dessie

Akalu

et al. 2020

International Journal of Hepatology

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Hepatocellular carcinoma (HCC) is an aggressive primary hepatic malignancy with a significant morbidity and mortality rate. Although chemotherapy along with surgical incision is believed to be an effective therapeutic approach, to date recurrence is being lifted a major concern. Thus, identifying another best therapeutic approach is becoming the main aim of physicians and scholars. In support of this, recently, several studies reported a significant observation of Sirtuin1 (SIRT1) overexpression in the malignant tumor cells, including HCC. As a result, they believed that overexpression of SIRT1 may have an effect on the progression of HCC by targeting growth and/or apoptotic controlling transcriptional factors/signaling pathways. Similarly, other reports confirmed that SIRT1 inhibition had a direct or indirect role in the control of tumor cell growth and metastasis. Therefore, inhibiting the expression and activity of SIRT1 might have a therapeutic effect to handle HCC. However, there are a limited number of reviews regarding the issue, and here, we summarized hepatocellular expression of SIRT1 and its role on HCC progression.

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SIRT1 in Secretory Organ Cancer

Cited by 26 publications

References 72 publications

Loss of SIRT4 promotes the self-renewal of Breast Cancer Stem Cells

Loss of SIRT4 promotes the self-renewal of Breast Cancer Stem Cells

The Role of Nicotinamide in Cancer Chemoprevention and Therapy

Hepatocellular Expression of SIRT1 and Its Effect on Hepatocellular Carcinoma Progression: A Future Therapeutic Perspective

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