umu.sePublikasjoner
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
TGF beta-induced invasion of prostate cancer cells is promoted by c-Jun-dependent transcriptional activation of Snail1
Uppsala Univ, Sci Life Lab, Ludwig Inst Canc Res, Uppsala, Sweden.
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
Uppsala Univ, Sci Life Lab, Ludwig Inst Canc Res, Uppsala, Sweden.
Uppsala Univ, Dept Immunol Genet & Pathol, Rudbeck Lab, Uppsala, Sweden.
Vise andre og tillknytning
2014 (engelsk)Inngår i: Cell Cycle, ISSN 1538-4101, E-ISSN 1551-4005, Vol. 13, nr 15, s. 2400-2414Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

High levels of transforming growth factor-beta (TGF beta) correlate with poor prognosis for patients with prostate cancer and other cancers. TGF beta is a multifunctional cytokine and crucial regulator of cell fate, such as epithelial to mesenchymal transition (EMT), which is implicated in cancer invasion and progression. TGF beta conveys its signals upon binding to type I and type II serine/threonine kinase receptors (T beta RI/II); phosphorylation of Smad2 and Smad3 promotes their association with Smad4, which regulates expression of targets genes, such as Smad7, p21, and c-Jun. TGF beta also activates the ubiquitin ligase tumor necrosis factor receptor-associated factor 6 (TRAF6), which associates with T beta RI and activates the p38 mitogen-activated protein kinase (MAPK) pathway. Snail1 is a key transcription factor, induced by TGF beta that promotes migration and invasion of cancer cells. In this study, we have identified a novel binding site for c-Jun in the promoter of the Snail1 gene and report that the activation of the TGF beta-TRAF6-p38 MAPK pathway promotes both c-Jun expression and its activation via p38a-dependent phosphorylation of c-Jun at Ser63. The TRAF6-dependent activation of p38 also leads to increased stability of c-Jun, due to p38-dependent inactivation of glycogen synthase kinase (GSK) 3 beta by phosphorylation at Ser9. Thus, our findings elucidate a novel role for the p38 MAPK pathway in stimulated cells, leading to activation of c-Jun and its binding to the promoter of Snail1, thereby triggering motility and invasiveness of aggressive human prostate cancer cells.

sted, utgiver, år, opplag, sider
2014. Vol. 13, nr 15, s. 2400-2414
Emneord [en]
c-Jun, invasion, p38 MAPK, prostate cancer, Smads, Snail1, TGF beta, TRAF6
HSV kategori
Identifikatorer
URN: urn:nbn:se:umu:diva-93495DOI: 10.4161/cc.29339ISI: 000340720900016OAI: oai:DiVA.org:umu-93495DiVA, id: diva2:761878
Tilgjengelig fra: 2014-11-09 Laget: 2014-09-23 Sist oppdatert: 2018-06-07bibliografisk kontrollert

Open Access i DiVA

Fulltekst mangler i DiVA

Andre lenker

Forlagets fulltekst

Personposter BETA

Gudey, Shyam KumarBergh, AndersLandström, Marene

Søk i DiVA

Av forfatter/redaktør
Gudey, Shyam KumarBergh, AndersLandström, Marene
Av organisasjonen
I samme tidsskrift
Cell Cycle

Søk utenfor DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric

doi
urn-nbn
Totalt: 264 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf