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Transforming growth...
Transforming growth factor-β promotes aggressiveness and invasion of clear cell renal cell carcinoma
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- Tumkur Sitaram, Raviprakash, 1974- (author)
- Umeå universitet,Urologi och andrologi,Medical Biosciences
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- Mallikarjuna, Pramod (author)
- Umeå universitet,Patologi
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- Landström, Maréne (author)
- Umeå universitet,Patologi
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- Ljungberg, Börje (author)
- Umeå universitet,Urologi och andrologi
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(creator_code:org_t)
- 2016-05-04
- 2016
- English.
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:24, s. 35917-35931
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Abstract
Subject headings
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- ccRCC
- ALK5
- pSmad2/3
- PAI-1
- TGF-β signaling pathway
Publication and Content Type
- ref (subject category)
- art (subject category)
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