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Transforming growth...
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Tumkur Sitaram, Raviprakash,1974-Umeå universitet,Urologi och andrologi,Medical Biosciences
(författare)
Transforming growth factor-β promotes aggressiveness and invasion of clear cell renal cell carcinoma
- Artikel/kapitelEngelska2016
Förlag, utgivningsår, omfång ...
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2016-05-04
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Impact Journals, LLC,2016
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electronicrdacarrier
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LIBRIS-ID:oai:DiVA.org:umu-120254
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-120254URI
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https://doi.org/10.18632/oncotarget.9177DOI
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Språk:engelska
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Sammanfattning på:engelska
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The molecular mechanisms whereby transforming growth factor-β (TGF-β) promotes clear cell renal cell carcinoma (ccRCC) progression is elusive. The cell membrane bound TGF-β type I receptor (ALK5), was recently found to undergo proteolytic cleavage in aggressive prostate cancer cells, resulting in liberation and subsequent nuclear translocation of its intracellular domain (ICD), suggesting that ALK5-ICD might be a useful cancer biomarker. Herein, the possible correlation between ALK5 full length (ALK5-FL) and ALK5-ICD protein, phosphorylated Smad2/3 (pSmad2/3), and expression of TGF-β target gene PAI-1, was investigated in a clinical ccRCC material, in relation to tumor grade, stage, size and cancer specific survival. Expression of ALK5-FL, ALK5-ICD, pSmad2/3 and PAI-1 protein levels were significantly higher in higher stage and associated with adverse survival. ALK5-ICD, pSmad2/3 and PAI-1 correlated with higher grade, and ALK5-FL, pSmad2/3 and PAI-1 protein levels were significantly correlated with larger tumor size. Moreover, the functional role of the TGF-β - ALK5-ICD pathway were investigated in two ccRCC cell lines by treatment with ADAM/MMP2 inhibitor TAPI-2, which prevented TGF-β-induced ALK5-ICD generation, nuclear translocation, as well as cell invasion. The present study demonstrated that canonical TGF-β Smad2/3 pathway and generation of ALK5-ICD correlates with poor survival and invasion of ccRCC in vitro.
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Mallikarjuna, PramodUmeå universitet,Patologi(Swepub:umu)prma0023
(författare)
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Landström, MaréneUmeå universitet,Patologi(Swepub:umu)mala0231
(författare)
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Ljungberg, BörjeUmeå universitet,Urologi och andrologi(Swepub:umu)bolj0001
(författare)
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Umeå universitetUrologi och andrologi
(creator_code:org_t)
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Ingår i:Oncotarget: Impact Journals, LLC7:24, s. 35917-359311949-2553
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