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
Pro-invasive Snail1 targets TGFbeta receptor I to promote epithelial to mesenchymal transition in prostate cancer
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap. (Landstrom group)
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap. (Landstrom group)
Ludwig Institute for Cancer Research, Uppsala.
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
Emneord [en]
Snail1
HSV kategori
Forskningsprogram
onkologi
Identifikatorer
URN: urn:nbn:se:umu:diva-108012OAI: oai:DiVA.org:umu-108012DiVA, id: diva2:850268
Forskningsfinansiär
Swedish Research CouncilSwedish Cancer SocietyKnut and Alice Wallenberg FoundationTilgjengelig fra: 2015-09-01 Laget: 2015-09-01 Sist oppdatert: 2018-06-07bibliografisk kontrollert
Inngår i avhandling
1. TRAF6, a key regulator of TGFβ-induced oncogenesis in prostate cancer
Åpne denne publikasjonen i ny fane eller vindu >>TRAF6, a key regulator of TGFβ-induced oncogenesis in prostate cancer
2015 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Prostate cancer is the most common cancer in men, with the incidence rapidly increasing in Europe over the past two decades. Reliable biomarkers for prostate cancer are currently unavailable. Thus, there is an urgent need for improved biomarkers to diagnose prostate cancer at an early stage and to determine the best treatment options. Higher expression of transforming growth factor-β (TGFβ) has been reported in patients with aggressive cancer.

TGFβ is a multifunctional cytokine that acts as a tumor suppressor during early tumor development, and as a tumor promoter at later stages of cancer. TGFβ signals through the canonical Smad or non-Smad cascade via TGFβ type II and type I receptors. The TGFβ signaling cascade is regulated by various post-translational modifications of its key components. The present investigation aimed to identify a potential function of TRAF6 in TGFβ-induced responses in prostate cancer.

The first two articles of this thesis unveil the proteolytic cleavage of TGFβ type I receptor (TβRI), and the biological importance of the liberated TβRI intracellular domain (TβRI-ICD) in the nucleus. We found that tumor necrosis factor receptor-associated factor 6 (TRAF6) polyubiquitinates TβRI, which leads to cleavage of TβRI by tumor necrosis factor alpha converting enzyme (TACE) in a protein kinase C zeta (PKCζ)-dependent manner. Following ectodomain shedding, TβRI undergoes a second cleavage by presenilin 1 (PS1), which liberates TβRI-ICD. TβRI-ICD translocates to the nucleus, where it regulates its own expression as well as expression of the pro-invasive gene Snail1, thereby promoting invasion. We further found that TβRI-ICD associates with Notch intracellular domain (NICD) to drive expression of the pro-invasive gene Snail1, as well as Notch1 ligand Jag1.

The third article provides evidence that TRAF6 promotes Lys63-linked polyubiquitination of TβRI at Lys178 in a TGFβ-dependent manner. TβRI polyubiquitination was found to be a prerequisite for TβRI nuclear translocation, and thus for regulation of the genes involved in cell cycle, differentiation, and invasion of prostate cancer cells.

In the fourth article we investigated the role of the pro-invasive gene Snail1 in TGFβ-induced epithelial-to-mesenchymal transition (EMT) in prostate cancer cells.

sted, utgiver, år, opplag, sider
Umeå: Umeå University, 2015. s. 55
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1739
Emneord
TβRI, TGFβ, TACE, TRAF6, PS1, PKCζ, TβRI-ICD, NICD, Smad, non-Smad, prostate cancer, Snail1, MMP, p300, p21, PAI1, ubiquitination, cleavage, ICD, invasion, HES1, signaling
HSV kategori
Forskningsprogram
patologi
Identifikatorer
urn:nbn:se:umu:diva-108014 (URN)978-91-7601-315-1 (ISBN)
Disputas
2015-09-25, Hörsal Betula, Norrlands Universitetssjukhus, Umeå, 09:00 (engelsk)
Opponent
Veileder
Forskningsfinansiär
Swedish Cancer SocietyThe Kempe FoundationsKnut and Alice Wallenberg Foundation
Tilgjengelig fra: 2015-09-04 Laget: 2015-09-01 Sist oppdatert: 2018-06-07bibliografisk kontrollert

Open Access i DiVA

Fulltekst mangler i DiVA

Personposter BETA

Gudey, Shyam KumarSundar, ReshmaLandström, Marene

Søk i DiVA

Av forfatter/redaktør
Gudey, Shyam KumarSundar, ReshmaLandström, Marene
Av organisasjonen

Søk utenfor DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric

urn-nbn
Totalt: 243 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