118 research outputs found
SIAH2 antagonizes TYK2-STAT3 signaling in lung carcinoma cells
Get PDFThe Janus tyrosine kinases JAK1-3 and tyrosine kinase-2 (TYK2) are frequently hyperactivated in tumors. In lung cancers JAK1 and JAK2 induce oncogenic signaling through STAT3. A putative role of TYK2 in these tumors has not been reported. Here, we show a previously not recognized TYK2-STAT3 signaling node in lung cancer cells. We reveal that the E3 ubiquitin ligase seven-in-absentia-2 (SIAH2) accelerates the proteasomal degradation of TYK2. This mechanism consequently suppresses the activation of STAT3. In agreement with these data the analysis of primary non-small-cell lung cancer (NSCLC) samples from three patient cohorts revealed that compared to lung adenocarcinoma (ADC), lung squamous cell carcinoma (SCC) show significantly higher levels of SIAH2 and reduced STAT3 phosphorylation levels. Thus, SIAH2 is a novel molecular marker for SCC. We further demonstrate that an activation of the oncologically relevant transcription factor p53 in lung cancer cells induces SIAH2, depletes TYK2, and abrogates the tyrosine phosphorylation of STAT1 and STAT3. This mechanism appears to be different from the inhibition of phosphorylated JAKs through the suppressor of cytokine signaling (SOCS) proteins. Our study may help to identify molecular mechanisms affecting lung carcinogenesis and potential therapeutic targets
Formule : Clause « canine » à insérer dans les conventions de séparation ou de divorce
No full textInternational audienc
Requête aux fins de modification de la résidence de l'enfant
No full textInternational audienceou d'un droit de visite et d'hébergement tenant compte de l'évolution professionnelle de l'un des parent
Catastrophe du tunnel du Mont-Blanc (24 mars 1999)
No full textInternational audienceUn traitement judiciaire et juridique exemplaire des violences involontaire
- …
