Loss of Notch1-dependent p21<i><sup>Waf1/Cip1</sup></i>expression influences the Notch1 outcome in tumorigenesis

Cialfi, Samantha; Palermo, Rocco; Manca, Sonia; Blasio, Carlo De; Romero, Paula Vargas; Checquolo, Saula; Bellavia, Diana; Uccelletti, Daniela; Saliola, Michele; D’Alessandro, Angelo; Zolla, L.; Gulino, Alberto; Screpanti, Isabella; Talora, Claudio

doi:10.4161/cc.29079

Cited by 33 publications

(36 citation statements)

References 56 publications

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“…The role of the Notch pathway in cancers has been determined according to the effect of Notch pathway on cell proliferation, migration, and invasion [22][23][24][25][26]. In the present study, we demonstrated that TRIM67 overexpression can upregulate Notch1, Jagged1, and NICD.…”

Section: Discussionsupporting

confidence: 58%

TRIM67 Promotes the Proliferation, Migration, and Invasion of Non-Small-Cell Lung Cancer by Positively Regulating the Notch Pathway

Jiang¹,

Ren²,

Xu³

et al. 2020

J. Cancer

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Tripartite motif-containing 67 (TRIM67), an E3 ubiquitin ligase, belongs to the TRIM protein family. The relationship between TRIM67 and tumorigenesis is not fully clear. Here, we elucidated TRIM67 function in non-small cell lung cancer (NSCLC). TRIM67 immunostaining results were correlated with clinicopathological features. Moreover, the function of TRIM67 in cultured NSCLC cells was evaluated by MTT, colony formation, and Transwell assays. TRIM67 expression was associated with tumor size, lymph node metastasis, p-TNM stage, cancer cell differentiation, and poor prognosis. We altered TRIM67 expression in A549 and H1299 cell lines, and the results showed that TRIM67 promoted cell proliferation, migration, invasion and EMT by positively regulating the Notch pathway. Collectively, the results showed that TRIM67 promotes NSCLC progression through the Notch pathway and that TRIM67 expression is associated with clinicopathological features, indicating that TRIM67 may play an important role in promoting the development of NSCLC and could be applied as not only an important prognostic biomarker but also a therapeutic target in NSCLC.

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Section: Discussionsupporting

confidence: 58%

TRIM67 Promotes the Proliferation, Migration, and Invasion of Non-Small-Cell Lung Cancer by Positively Regulating the Notch Pathway

Jiang¹,

Ren²,

Xu³

et al. 2020

J. Cancer

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“…These results suggest that TQ inhibits the expression of cyclinD1, CDK2 and Bcl-2 while accelerating the expression of p21 and Bax, at least in part via repression of Notch signaling. A number of studies have shown that activated Notch can modulate expression of p21 and Bcl-2 [ 45 – 46 ], suggesting that p21 and Bcl-2 are downstream of TQ- induced Notch inhibition, and suggesting that TQ may restore normal proliferation and apoptosis by downregulating the Notch pathway.…”

Section: Discussionmentioning

confidence: 99%

TQ inhibits hepatocellular carcinoma growthin vitroandin vivovia repression of Notch signaling

Zhao

et al. 2015

Oncotarget

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Thymoquinone (TQ) has been reported to possess anti-tumor activity in various types of cancer. However, its effects and molecular mechanism of action in hepatocellular carcinoma (HCC) are still not completely understood. We observed that TQ inhibited tumor cell growth in vitro, where treatment with TQ arrested the cell cycle in G1 by upregulating p21 and downregulating cyclinD1 and CDK2 expression; moreover, TQ induced apoptosis by decreasing expression of Bcl-2 and increasing expression of Bax. Simultaneously, TQ demonstrated a suppressive impact on the Notch pathway, where overexpression of NICD1 reversed the inhibitory effect of TQ on cell proliferation, thereby attenuating the repressive effects of TQ on the Notch pathway, cyclinD1, CDK2 and Bcl-2, and also diminishing upregulation of p21 and Bax. In a xenograft model, TQ inhibited HCC growth in nude mice; this inhibitory effect in vivo, as well as of HCC cell growth in vitro, was associated with a discernible decline in NICD1 and Bcl-2 levels and a dramatic rise in p21 expression. In conclusion, TQ inhibits HCC cell growth by inducing cell cycle arrest and apoptosis, achieving these effects by repression of the Notch signaling pathway, suggesting that TQ represents a potential preventive or therapeutic agent in HCC patients.

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“…In human primary neonatal keratinocytes (NHEKs) it was found that arsenic causes cumulative disruptions to epigenetic regulation of miR-34a expression and alteration of its target histone deacetylase SIRT1 protein, by disrupting the profile of histone acetylation and DNA methylation and by suppressing SIRT1 activity [77]. In a separate report, it was demonstrated that acute exposure of HaCaT keratinocytes to arsenite, p21waf1/Cip1 was up-regulated and Notch1 was down-regulated, favoring the Notch1 contribution on arsenic-induced keratinocyte transformation and cancerogenesis [78]. In addition, it was reported that arsenite induced epigenetic silencing of let-7c via Ras/NF-κB that is involved in the acquisition of cancer stem cell-like properties and neoplastic transformation of HaCaT cells, which contribute to the tumorigenesis [79].…”

Section: Discussionmentioning

confidence: 99%

Arsenic-exposed Keratinocytes Exhibit Differential microRNAs Expression Profile; Potential Implication of miR-21, miR-200a and miR-141 in Melanoma Pathway

Gonzalez

Lema

Kirken

et al. 2015

CCAND

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Long-term exposure to arsenic has been linked to cancer in different organs and tissues, including skin. Here, non-malignant human keratinocytes (HaCaT) were exposed to arsenic and its effects on microRNAs (miRNAs; miR) expression were analyzed via miRCURY LNA array analyses. A total of 30 miRNAs were found differentially expressed in arsenic-treated cells, as compared to untreated controls. Among the up-regulated miRNAs, miR-21, miR-200a and miR-141, are well known to be involved in carcinogenesis. Additional findings confirmed that those three miRNAs were indeed up-regulated in arsenic-stimulated keratinocytes as demonstrated by quantitative PCR assay. Furthermore, bioinformatics analysis of both potential cancer-related pathways and targeted genes affected by miR-21, miR-200a and/or miR-141 was performed. Results revealed that miR-21, miR-200a and miR-141 are implicated in skin carcinogenesis related with melanoma development. Conclusively, our results indicate that arsenic-treated keratinocytes exhibited alteration in the miRNAs expression profile and that miR-21, miR-200a and miR-141 could be promising early biomarkers of the epithelial phenotype of cancer cells and they could be potential novel targets for melanoma therapeutic interventions.

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Loss of Notch1-dependent p21^Waf1/Cip1expression influences the Notch1 outcome in tumorigenesis

Cited by 33 publications

References 56 publications

TRIM67 Promotes the Proliferation, Migration, and Invasion of Non-Small-Cell Lung Cancer by Positively Regulating the Notch Pathway

TRIM67 Promotes the Proliferation, Migration, and Invasion of Non-Small-Cell Lung Cancer by Positively Regulating the Notch Pathway

TQ inhibits hepatocellular carcinoma growthin vitroandin vivovia repression of Notch signaling

Arsenic-exposed Keratinocytes Exhibit Differential microRNAs Expression Profile; Potential Implication of miR-21, miR-200a and miR-141 in Melanoma Pathway

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Loss of Notch1-dependent p21Waf1/Cip1expression influences the Notch1 outcome in tumorigenesis

Cited by 33 publications

References 56 publications

TRIM67 Promotes the Proliferation, Migration, and Invasion of Non-Small-Cell Lung Cancer by Positively Regulating the Notch Pathway

TRIM67 Promotes the Proliferation, Migration, and Invasion of Non-Small-Cell Lung Cancer by Positively Regulating the Notch Pathway

TQ inhibits hepatocellular carcinoma growthin vitroandin vivovia repression of Notch signaling

Arsenic-exposed Keratinocytes Exhibit Differential microRNAs Expression Profile; Potential Implication of miR-21, miR-200a and miR-141 in Melanoma Pathway

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Loss of Notch1-dependent p21^Waf1/Cip1expression influences the Notch1 outcome in tumorigenesis