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TRAF6 function as a...
TRAF6 function as a novel co-regulator of Wnt3a target genes in prostate cancer
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- Aripaka, Karthik (författare)
- Umeå universitet,Patologi
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- Gudey, Shyam Kumar, 1982- (författare)
- Umeå universitet,Patologi
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- Zang, Guangxiang (författare)
- Umeå universitet,Patologi
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- Schmidt, Alexej (författare)
- Umeå universitet,Patologi
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- Åhrling, Samaneh Shabani (författare)
- Umeå universitet,Patologi
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- Österman, Lennart (författare)
- Umeå universitet,Medicinsk och klinisk genetik
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- Bergh, Anders (författare)
- Umeå universitet,Patologi
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- von Hofsten, Jonas (författare)
- Umeå universitet,Umeå centrum för molekylär medicin (UCMM),Institutionen för integrativ medicinsk biologi (IMB)
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- Landström, Maréne (författare)
- Umeå universitet,Patologi
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(creator_code:org_t)
- Elsevier, 2019
- 2019
- Engelska.
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 45, s. 192-207
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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http://www.thelancet...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: Tumour necrosis factor receptor associated factor 6 (TRAF6) promotes inflammation in response to various cytokines. Aberrant Wnt3a signals promotes cancer progression through accumulation of β-Catenin. Here we investigated a potential role for TRAF6 in Wnt signaling.Methods: TRAF6 expression was silenced by siRNA in human prostate cancer (PC3U) and human colorectal SW480 cells and by CRISPR/Cas9 in zebrafish. Several biochemical methods and analyses of mutant phenotype in zebrafish were used to analyse the function of TRAF6 in Wnt signaling.Findings: Wnt3a-treatment promoted binding of TRAF6 to the Wnt co-receptors LRP5/LRP6 in PC3U and LNCaP cells in vitro. TRAF6 positively regulated mRNA expression of β-Catenin and subsequent activation of Wnt target genes in PC3U cells. Wnt3a-induced invasion of PC3U and SW480 cells were significantly reduced when TRAF6 was silenced by siRNA. Database analysis revealed a correlation between TRAF6 mRNA and Wnt target genes in patients with prostate cancer, and high expression of LRP5, TRAF6 and c-Myc correlated with poor prognosis. By using CRISPR/Cas9 to silence TRAF6 in zebrafish, we confirm TRAF6 as a key molecule in Wnt3a signaling for expression of Wnt target genes.Interpretation: We identify TRAF6 as an important component in Wnt3a signaling to promote activation of Wnt target genes, a finding important for understanding mechanisms driving prostate cancer progression.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- beta-Catenin
- LRP5
- Prostate cancer
- TRAF6
- Wnt3a
- Zebrafish
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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