Structure du récepteur Smoothened

Ruat, Martial; Hoch, Lucile; Faure, Hélène; Rognan, Didier

doi:10.1051/medsci/20132910012

Cited by 3 publications

(4 citation statements)

References 33 publications

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“…SMO is a major component involved in SHH signaling transduction, which can be coupled with G protein‐coupled receptors (GPCRs) to inhibit the activity of suppressor of fused protein (SUFU) and GLI family of transcription factors. When the SHH signaling pathway is activated, PTCH‐1 , which destabilizes SMO and inhibits its activity, is degraded, leading to the activation of G‐protein coupled receptor (GPCR)/ SMO activity 25 . This promotes the dissociation of GLI from its inhibitor protein SUFU, resulting in the release and transport of GLI into the nucleus, triggering downstream target gene expression and activating cellular functions 26 .…”

Section: Discussionmentioning

confidence: 99%

“…When the SHH signaling pathway is activated, PTCH‐1 , which destabilizes SMO and inhibits its activity, is degraded, leading to the activation of G‐protein coupled receptor (GPCR)/ SMO activity. 25 This promotes the dissociation of GLI from its inhibitor protein SUFU, resulting in the release and transport of GLI into the nucleus, triggering downstream target gene expression and activating cellular functions. 26 However, our results revealed a significant decrease in SMO and GLI‐1 protein levels in tumor tissues, suggesting that Rab23 plays a negative regulatory role in the SHH signaling pathway and can suppress tumor growth in HCC.…”

Section: Discussionmentioning

confidence: 99%

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Downregulation of Rab23 inhibits hepatocellular carcinoma by repressing SHH signaling pathway

Liu,

Zang,

Huang

et al. 2023

Cancer Reports

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Hepatocellular carcinoma (HCC) is the sixth most common malignant tumors and the third leading cause of cancer‐related death worldwide. As an oncogene, Rab23 has been shown to be significantly related to the growth and migration of hepatocellular carcinoma in both in vitro and in vivo studies, but its underlying mechanism remains obscure. In the present study, we examined the effect of inhibiting Rab23 expression on the pathological progression of HCC. The correlation between liver Rab23 gene expression and survival probability in human HCC patients was analyzed using the TCGA database and CPTAC database. Rab23 knockdown hepatocellular carcinoma cell line was generated through lentiviral transduction, then we established a nude HCC xenograft model by subcutaneously implanting the transfected cells. The analysis of gene and protein expression was carried out using Western blot or RT‐qPCR, respectively. Flow cytometry analysis was used to detect the level of apoptosis. The expression levels of key proteins involved in the Sonic Hedgehog (SHH) signaling pathway were assessed. The results showed that HCC patients with low levels of hepatic Rab23 mRNA and protein had a better survival tendency than those with higher levels of Rab23. Cell proliferations were reduced and apoptosis levels were increased after Knocking down Rab23 in HCC cell lines. Furthermore, in vivo studies have demonstrated that suppression of the Rab23 gene results in decreased tumor size, proliferation rate, and reduced levels of SHH‐related proteins Smoothened and GLI‐1. The above results suggest that Rab23 is involved in the pathological progression of HCC as an important regulator of the SHH signaling pathway, which also provides an important research basis for new therapeutic strategies for HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Downregulation of Rab23 inhibits hepatocellular carcinoma by repressing SHH signaling pathway

Liu,

Zang,

Huang

et al. 2023

Cancer Reports

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“…C'est pourquoi nous venons d'invalider in vivo dans les CSN adultes la protéine membranaire Patched, suppresseur de tumeurs et récepteur de Shh [9]. En l'absence de Shh, Patched réprime l'activité de Smoothened, l'élément clé de la transmission du signal Shh et une cible thérapeutique potentielle [10,11]. Si Patched n'est plus fonctionnel, la répression qu'il exerce normalement sur Smoothened est levée, ce qui conduit à l'activation endogène de la voie et à l'induction de la transcription du gène cible Gli1 dont le niveau d'expression reflète l'activité de la voie ( Figure 1A [6,16].…”

Section: Sonic Hedgehog Contrôle Le Devenir Des Csnunclassified

Division symétrique ou division asymétrique : Sonic Hedgehog contrôle le destin des cellules souches neurales adultes

2014

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“…Hedgehog interacting protein (HHIP) binds to IHH, DHH and SHH to inhibit HH signaling pathway [25-27]. The upregulation of HH signaling pathway is associated with decreasing expression of HHIP in human cancers [28-30].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of HHIP Promoter Methylation Suppresses Human Gastric Cancer Cell Proliferation and Migration

Zuo

Qian

et al. 2018

Cell Physiol Biochem

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Background/Aims: Human hedgehog-interacting protein (HHIP) is a negative regulator of the hedgehog (HH) signaling pathway. It is deregulated in gastric cancer. The underlying molecular mechanism of HHIP-induced inhibition of HH signaling remains to be determined. Methods: A lentiviral HHIP expression vector (“LV-HHIP”) was established to exogenously over-express HHIP in gastric cancer cells. HHIP protein and mRNA were tested by Western blotting assay and quantitative real-time PCR assay, respectively. Cell survival was tested by the Cell Counting Kit-8 (CCK-8) assay. Cell proliferation was examined by the BrdU ELISA assay and [H³] Thymidine DNA incorporation assay. Cell invasion and migration were tested by the phagokinetic track assay and the “Transwell” assay. The bisulfite-sequencing PCR was applied to test HHIP promoter methylation. Results: In the established (AGS cell line) and primary human gastric cancer cells, LV-HHIP transfection increased HHIP expression and inhibited cancer cell survival and proliferation as well as cell migration and invasion. Furthermore, LV-HHIP significantly attenuated promoter methylation of the endogenous HHIP gene in AGS cells, causing it upregulation. Inhibition of methylation by 5-aza-dc similarly induced HHIP expression in gastric cancer cells, which inhibited cancer cell proliferation and migration. Conclusions: Our results suggest that inhibition of HHIP promoter methylation can efficiently inhibit human gastric cancer cell proliferation and migration.

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Structure du récepteur Smoothened

Cited by 3 publications

References 33 publications

Downregulation of Rab23 inhibits hepatocellular carcinoma by repressing SHH signaling pathway

Downregulation of Rab23 inhibits hepatocellular carcinoma by repressing SHH signaling pathway

Division symétrique ou division asymétrique : Sonic Hedgehog contrôle le destin des cellules souches neurales adultes

Inhibition of HHIP Promoter Methylation Suppresses Human Gastric Cancer Cell Proliferation and Migration

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