Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence

Perciato, Maria Luna; Alajati, Abdullah; Chen, Jing Jing; Gerber, Hermeto; Dimitrov, Milen; Rinaldi, Andrea; Delaleu, Nicolas; Pasquini, Emiliano; D’Antuono, Rocco; Pinton, Sandra; Losa, Marco; Gnetti, Letizia; Arribas, Alberto J.; Fraering, Patrick C.; Bertoni, Francesco; Nepveu, Alain; Alimonti, Andrea

doi:10.1038/ncomms13719

Cited by 38 publications

(37 citation statements)

References 65 publications

(92 reference statements)

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“…29 Recently, one study identified that inhibition of Notch pathway arrested PTEN-deficient advanced prostate cancer via enhancing p27-driven cellular senescence. 30 Studies investigated the function of Notch signaling pathway in prostate cancer. 31 However, it is unclear whether Notch pathway is associated with EMT in prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Activation of Notch pathway is linked with epithelial-mesenchymal transition in prostate cancer cells

et al. 2017

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Section: Introductionmentioning

confidence: 99%

Activation of Notch pathway is linked with epithelial-mesenchymal transition in prostate cancer cells

et al. 2017

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“…For example, Revandkar et al . demonstrated that PTEN‐deficient PC was arrested by suppression of Notch signaling pathway. Curcumin inhibited PC cell survival through Notch‐1 signaling pathway .…”

Section: Discussionmentioning

confidence: 99%

Knockdown of LncRNA GHET1 suppresses prostate cancer cell proliferation by inhibiting HIF‐1α/Notch‐1 signaling pathway via KLF2

Zhu

Tong

Wu³

et al. 2019

BioFactors

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Prostate cancer (PC) is one of the most common cancers in male groups worldwide. Long noncoding RNAs (LncRNAs) are reported to be dysregulated in a variety of cancers, including PC. This study aimed to explore the role of LncRNA GHET1 in the pathogenesis of PC. RT-qPCR was carried out to examine the relative expression level of GHET1 in PC patients. In vitro, GHET1 siRNA (si-GHET1) was used to investigate the biological role of GHET1 in PC cell lines. Cell proliferation was detected by CCK-8 and colony formation assay, while cell cycle and cell apoptosis were analyzed using flow cytometry. Moreover, western blot was carried out to measure the protein expression levels of KLF2 and HIF-1α/Notch-1 signal pathway. We found that GHET1 showed higher expression in PC tissues and had a negative correlation with KLF2 expression. Knockdown of GHET1 significantly suppressed the cell proliferation, induced cell cycle arrest at G0/G1 phase and promoted cell apoptosis. Additionally, si-GHET1 transfection induced KLF2 upregulation and HIF-1α/Notch-1 signal pathway suppression, which could be rescued by si-KLF2 transfection. These results suggest the key role of GHET1 in PC progression. Moreover, GHET1 might be explored to be a potential target for clinical treatment of PC.

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“…P21 Waf1/Cip1 and p27 are widely recognised targets of Notch signaling and contribute to proliferation regulation (Devgan, Mammucari, Millar, Brisken, & Dotto, ; Tanaka et al, ; Yu et al, ). Notch signaling inhibition by genetic and pharmacological methods caused proliferation suppression and p27‐mediated cellular senescence responses (Revandkar et al, ). Notch signaling promotes the cell cycle by inhibiting p27Kip1 expression both transcriptionally and post‐translationally (Del Debbio et al, ).…”

Section: Discussionmentioning

confidence: 99%

Notch signaling inhibition induces G0/G1 arrest in murine Leydig cells

Feng

Wen

et al. 2019

Andrologia

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As a highly evolutionarily conserved signaling pathway, Notch widely participates in cell-fate decisions and the development of various tissues and organs. In male reproduction, research on the Notch signaling pathway has mainly concentrated on germ cells and Sertoli cells. Leydig cells are the primary producers of testosterone and play important roles in spermatogenesis and maintaining secondary sexual characteristics. In this study, we used TM3 cells, a murine adult Leydig cell line, to investigate the expression profiles of Notch receptors and ligands and observe the effect of Notch signaling on the proliferation of TM3 cells. We found that Notch 1-3 and the ligands Dll-1 and Dll-4 were expressed in TM3 cells, Notch 1-3 and the ligand Dll-1 were expressed in testis interstitial Leydig cells, and Notch signaling inhibition suppressed the proliferation of TM3 cells and induced G0/G1 arrest. Inhibition of Notch signaling increased the expression of p21 Waf1/Cip1 and p27. Overall, our results suggest that Notch inhibition suppresses the proliferation of TM3 cells and P21 Waf1/Cip1 , and p27 may contribute to this process. K E Y W O R D Scell proliferation, Leydig cell, P21 Waf1/Cip1 , P27

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Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence

Cited by 38 publications

References 65 publications

Activation of Notch pathway is linked with epithelial-mesenchymal transition in prostate cancer cells

Activation of Notch pathway is linked with epithelial-mesenchymal transition in prostate cancer cells

Knockdown of LncRNA GHET1 suppresses prostate cancer cell proliferation by inhibiting HIF‐1α/Notch‐1 signaling pathway via KLF2

Notch signaling inhibition induces G0/G1 arrest in murine Leydig cells

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