Sirtuin 7 promotes colorectal carcinoma proliferation and invasion through the inhibition of E-cadherin

Deng, Zhigang; Wang, Xingbiao; Long, Xuan; Liu, Wanzhong; Xiang, Chunhua; Bao, Feng; Wang, Dong

doi:10.3892/etm.2017.5673

Cited by 10 publications

(14 citation statements)

References 28 publications

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“…EMT can be driven by Snail/Slug, Twist (Twist1)/Twist2 and Zeb1/Zeb2 transcription factors with the ability to suppress E-cadherin and activate N-cadherin and vimentin directly or indirectly ( 43 , 44 ). Previous studies have revealed the role of SIRT7 in activation of EMT in several cancers ( 16 , 20 , 45 , 46 ). To further clarify the association between SIRT7 and EMT in NSCLC cells, the present study determined the effects of SIRT7 overexpression or knockdown on the expression of EMT-related molecules in human NSCLC cells.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, SIRT7-induced activation of AKT/ERK1/2 signaling may participate in SIRT7-induced upregulation of Snail and Slug in NSCLC cells by positively modulating their stability through the AKT/ERK1/2-GSK3β-Snail/Slug axis. Notably, emerging evidence has revealed that SIRT7 can directly bind to the promoter of E-cadherin to promote H3K18Ac deacetylation, resulting in inhibition of E-cadherin transcription ( 45 , 46 ), which prompted us to infer that SIRT7 may also directly suppress E-cadherin expression of NSCLC cells in a chromatin-remodeling manner.…”

Section: Discussionmentioning

confidence: 99%

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Sirtuin 7 promotes non‑small cell lung cancer progression by facilitating G1/S phase and epithelial‑mesenchymal transition and activating AKT and ERK1/2 signaling

et al. 2020

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Increasing evidence has indicated the roles of sirtuin 7 (SIRT7) in numerous human cancers. However, the effects and the clinical significance of SIRT7 in human lung cancer is largely unknown. The present research demonstrated that SIRT7 was increased in human lung cancer tumor tissues. SIRT7 upregulation was associated with clinicopathological characteristics of lung cancer malignancy including positive lymph node metastasis, high pathologic stage and large tumor size. SIRT7 was also upregulated in human non-small cell lung cancer (NSCLC) cell lines. Furthermore SIRT7-overexpressed A549 (A549-SIRT7) and SIRT7-knocked down H292 (H292-shSIRT7) human NSCLC cell lines were established. Using these NSCLC cells and xenograft mouse models, it was revealed that SIRT7 overexpression markedly promoted growth and G1 to S cell cycle phase transition as well as migration, invasion and distant lung metastasis in A549 NSCLC cells, whereas SIRT7 knockdown suppressed these processes in H292 NSCLC cells. Mechanistically, in A549 NSCLC cells, SIRT7 overexpression significantly activated not only protein kinase B (AKT) signaling but also extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. SIRT7 overexpression also significantly downregulated cyclin-dependent kinase (CDK) inhibitors including p21 and p27 as well as upregulated cyclins including cyclin D1 and cyclin E1, and CDKs including CDK2 and CDK4. Notably, the epithelial-mesenchymal transition (EMT) process of A549 NSCLC cells was facilitated by SIRT7 overexpression, as evidenced by E-cadherin epithelial marker downregulation and mesenchymal markers (N-cadherin, vimentin, Snail and Slug) upregulation. In addition, SIRT7 knockdown in H292 NSCLC cells exhibited the opposite regulatory effects. Moreover, inhibition of AKT signaling abated the promoting effects of SIRT7 in NSCLC cell proliferation and EMT progression. The present data indicated that SIRT7 accelerated human NSCLC cell growth and metastasis possibly by promotion of G1 to S-phase transition and EMT through modulation of the expression of G1-phase checkpoint molecules and EMT markers as well as activation of AKT and ERK1/2 signaling. SIRT7 could be an innovative potential target for human NSCLC therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sirtuin 7 promotes non‑small cell lung cancer progression by facilitating G1/S phase and epithelial‑mesenchymal transition and activating AKT and ERK1/2 signaling

et al. 2020

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“…Similarly in oral squamous cell carcinoma (OSCC) cells, SIRT7 is responsible for induction of E-cadherin expression and suppression of N-cadherin, Vimentin and MMP7 (27). In contrast, SIRT7 was found to promote mesenchymal transition in the context of oncogenic roles of SIRT7 in colorectal and prostate cancers, primarily by suppressing E-Cadherin expression (28)(29)(30). However, all these studies were done in epithelial cells, which have already undergone a prior process of cell transition to achieve the cancerous state.…”

Section: Discussionmentioning

confidence: 99%

“…SIRT7 was found to suppress EMT in oral squamous cells, carcinoma cells, and breast cancer cells by promoting SMAD4 deacetylation, leading to increase of E-cadherin and down regulation of N-cadherin and Vimentin (26,27). In contrast, SIRT7 promoted EMT in prostate and colorectal cancer cells by suppressing E-cadherin expression (28)(29)(30). However, the overall role of SIRT7 in cellular plasticity was not demonstrated and a decrease in tumor size after SIRT7 knockdown was not very appreciable.…”

Section: Introductionmentioning

confidence: 94%

Sirtuin 7 Promotes Mesenchymal to Epithelial Transition by β-Catenin Redistribution and Stabilization

Kiran

Ramakrishna

2020

Front. Oncol.

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SIRT7 belongs to the family of "NAD+ dependent deacetylases" called Sirtuins. In the present work we report a novel role of SIRT7 in regulating cellular polarity. SIRT7 overexpression in immortalized mouse fibroblasts (NIH3T3) induced epithelial transition. This transition was accompanied by typical N-to E-cadherin transition, stabilization of β-catenin, and the downregulation of transcription factors responsible for maintenance of mesenchymal phenotype (Snail, Slug, and Zeb1). Interestingly, a subpopulation of cells overexpressing SIRT7 exhibited an intermediate stage between mesenchymal and epithelial characters. Transformed epithelial cells showed a loss of heterochromatisation as evidenced by a loss of HP1α and H3K9 dimethylation staining. In conclusion, we report a role of SIRT7 in mesenchymal cells, which may have implications for health and disease.

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“…225 Currently, SIRT7 has been purported to have oncogenic potential through its implications in defending cancer cells from genotoxicity. Colorectal, ovarian, and liver cancer cells have all shown increased expression levels of SIRT7, 226–229 lending to the likelihood of the enzyme’s function as a tumor promoter. While further study is necessary to understand its direct implications in cancer development, the diverse functional profile of SIRT7 highlights numerous possibilities for the enzyme’s involvement in carcinogenesis.…”

Section: Nad Functions As Substratementioning

confidence: 99%

NAD metabolism in aging and cancer

Kincaid

Berger

2020

Exp Biol Med (Maywood)

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NAD+ and its derivatives NADH, NADP+, and NADPH are essential cofactors in redox reactions and electron transport pathways. NAD serves also as substrate for an extensive series of regulatory enzymes including cyclic ADP-ribose hydrolases, mono(ADP-ribosyl)transferases, poly(ADP-ribose) polymerases, and sirtuin deacetylases which are O-acetyl-ADP-ribosyltransferases. As a result of the numerous and diverse enzymes that utilize NAD as well as depend on its synthesis and concentration, significant interest has developed in its role in a variety of physiologic and pathologic processes, and therapeutic initiatives have focused both on augmenting its levels as well as inhibiting some of its pathways. In this article, we examine the biosynthesis of NAD, metabolic processes in which it is involved, and its role in aging, cancer, and other age-associated comorbidities including neurodegenerative, cardiovascular, and metabolic disorders. Therapeutic interventions to augment and/or inhibit these processes are also discussed. Impact statement NAD is a central metabolite connecting energy balance and organismal growth with genomic integrity and function. It is involved in the development of malignancy and has a regulatory role in the aging process. These processes are mediated by a diverse series of enzymes whose common focus is either NAD’s biosynthesis or its utilization as a redox cofactor or enzyme substrate. These enzymes include dehydrogenases, cyclic ADP-ribose hydrolases, mono(ADP-ribosyl)transferases, poly(ADP-ribose) polymerases, and sirtuin deacetylases. This article describes the manifold pathways that comprise NAD metabolism and promotes an increased awareness of how perturbations in these systems may be important in disease prevention and/or progression.

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Sirtuin 7 promotes colorectal carcinoma proliferation and invasion through the inhibition of E-cadherin

Cited by 10 publications

References 28 publications

Sirtuin 7 promotes non‑small cell lung cancer progression by facilitating G1/S phase and epithelial‑mesenchymal transition and activating AKT and ERK1/2 signaling

Sirtuin 7 promotes non‑small cell lung cancer progression by facilitating G1/S phase and epithelial‑mesenchymal transition and activating AKT and ERK1/2 signaling

Sirtuin 7 Promotes Mesenchymal to Epithelial Transition by β-Catenin Redistribution and Stabilization

NAD metabolism in aging and cancer

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