AK-1, a specific SIRT2 inhibitor, induces cell cycle arrest by downregulating Snail in HCT116 human colon carcinoma cells

Cheon, Min Gyeong; Kim, Wootae; Choi, Minsu; Kim, Ja-Eun

doi:10.1016/j.canlet.2014.10.012

Cited by 62 publications

(37 citation statements)

References 46 publications

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“…SIRT2 over-expression in cells prolongs cell division. SIRT2 inhibitor induces G1 arrest in HCT116 colon cancer cells ( Cheon et al, 2015 ). Furthermore, it is reported that SIRT2 is associated with myelination and, as a potential tumor suppressor, plays a crucial role in the tumor inhibition ( Beirowski et al, 2011 ;Kim et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

SIRT2 suppresses non-small cell lung cancer growth by targeting JMJD2A

Jiang

Shen

et al. 2015

Biological Chemistry

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Lung cancer has been the most prolific cancer in China - as in the rest of the world - with a high death rate and low 5-year survival rate. Previous evidence showed that JMJD2A is over-expressed in human non-small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues, and that high level of JMJD2A predicts poor overall and disease-free survival. However, the mechanism by which JMJD2A is regulated in human NSCLC is not fully understood. In the present study, we identified that the SIRT2 as an anti-oncogenic protein in NSCLC was down-regulated. JMJD2A as a target of SIRT2 was negatively correlated with SIRT2 level in NSCLC. SIRT2 bound to the promoter region of JMJD2A and negatively regulated JMJD2A expression. In addition, we found that SIRT2 inhibited NSCLC cells proliferation, colony formation and tumor growth in vitro and in vivo in a JMJD2A-dependent manner. In summary, our findings implicate that SIRT2 suppresses non-small cell lung cancer growth through targeting JMJD2A and SIRT2 activator may serve as candidate drug for NSCLC therapy.

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Section: Introductionmentioning

confidence: 99%

SIRT2 suppresses non-small cell lung cancer growth by targeting JMJD2A

Jiang

Shen

et al. 2015

Biological Chemistry

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“…It is contrary to the acknowledged blocking effect (40,45). Drug-induced downregulation of Snail was connected with upregulation of p21 and G1 phase arrest (46). However, those who first found the repression effect of Snail on p21 (47), already indicate it may be dependend on the type of the cell line.…”

Section: Discussionmentioning

confidence: 89%

SNAILs promote G1 phase in selected cancer cells

Xue

Zhou

et al. 2015

Int J Oncol

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Abstract. Cells can acquire a stem-like cell phenotype through epithelial-mesenchymal transition (EMT). However, it is not known which of the stem-like cancer cells are generated by these phenotype transitions. We studied the EMT-inducing roles of SNAILs (the key inducers for the onset of EMT) in selected cancer cells (lung cancer cell line with relatively stable genome), in order to provide more implications for the investigation of EMT-related phenotype transitions in cancer. However, SNAILs fail to induce completed EMT. In addition, we proved that Snail accelerates the early G1 phase whereas Slug accelerates the late G1 phase. Blocking G1 phase is one of the basic conditions for the onset of EMT-related phenotype transitions (e.g., metastasis, acquring stemness). The discovery of this unexpected phenomenon (promoting G1 phase) typically reveals the heterogeneity of cancer cells. The onset of EMT-related phenotype transitions in cancer needs not only the induction and activation of SNAILs, but also some particular heredity alterations (genetic or epigenetic alterations, which cause heterogeneity). The new connection between heredity alteration (heterogeneity) and phenotype transition suggests a novel treatment strategy, the heredity alteration-directed specific target therapy. Further investigations need to be conducted to study the relevant heredity alterations. IntroductionCancer stem cell (CSC) is a cell within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor (1). Although it has been proven that epithelial-mesenchymal transition (EMT) can generate cells with stem cell properties (2), it is still unknown which of the stem-like cancer cells are generated by these phenotype transitions.The function of Snail genes is best known for induction of EMT. Both in development and during carcinoma progression, Snail1 (Snail) is expressed at the onset of the transition, whereas Snail2 (Slug), Zeb genes, E47 and Twist are subsequently induced to maintain the migratory mesenchymal state (3). As transcriptional repressors, Snail and Slug can regulate the expression of genes mediating therapeutic resistance and acquiring of stem-like phenotype in ovarian cancer cells (4).Snail and Slug have complicated interactions with many key molecules. Snail can cause functional deficiency of p53 in tumor cells with mutant KRAS (5). We know GSK3β, the downstream molecule of Akt (6), can phosphorylate Snail to cause the degradation or the nuclear export of Snail (7). However, KRAS can interact with the PI3K/Akt pathway (8), and then affect GSK3β. Slug can escape degradation when p53 is mutant in lung cancer (9). In addition, the experssion of Slug can be regulated by mutant KRAS in colon cancer cells (10). Snail and Slug are also connected to other key molecules (e.g., EGFR, ERCC1) (11-13).Certain key molecules, including KRAS, p53, EGFR, ERCC1, are all connected to EMT (11,[14][15][16] and stem cell biology (17)(18)(19)(20). This makes the SNAIL-related ph...

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“…The mammalian sirtuin family has seven proteins, SIRT1-SIRT7, that are highly conserved ADP-ribosyltransferases or NAD þ -dependent class III deacetylase proteins [17]. Various studies have reported different subcellular localizations for each family member, with SIRT1 and SIRT2 being found in both the nucleus and cytoplasm, SIRT3-SIRT5 in the mitochondria, and SIRT6 and SIRT7 in the nucleus [18,19].…”

Section: Introductionmentioning

confidence: 99%