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VHL status regulate...
VHL status regulates transforming growth factor-β signaling pathways in renal cell carcinoma
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- Mallikarjuna, Pramod (författare)
- Umeå universitet,Patologi
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- Tumkur Sitaram, Raviprakash, 1974- (författare)
- Umeå universitet,Patologi,Urologi och andrologi,ML
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- Landström, Maréne (författare)
- Umeå universitet,Patologi
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- Ljungberg, Börje (författare)
- Umeå universitet,Urologi och andrologi
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(creator_code:org_t)
- 2018-03-27
- 2018
- Engelska.
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:23, s. 16297-16310
- 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.oncotarge...
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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
- To evaluate the role of pVHL in the regulation of TGF-β signaling pathways in clear cell renal cell carcinoma (ccRCC) as well as in non-ccRCC; the expression of pVHL, and the TGF-β pathway components and their association with clinicopathological parameters and patient’s survival were explored. Tissue samples from 143 ccRCC and 58 non-ccRCC patients were examined by immunoblot. ccRCC cell lines were utilized for mechanistic in-vitro studies. Expression levels of pVHL were significantly lower in ccRCC compared with non-ccRCC. Non-ccRCC and ccRCC pVHL-High expressed similar levels of pVHL. Expression of the TGF-β type I receptor (ALK5) and intra-cellular domain were significantly higher in ccRCC compared with non-ccRCC. In non-ccRCC, expressions of ALK5-FL, ALK5-ICD, pSMAD2/3, and PAI-1 had no association with clinicopathological parameters and survival. In ccRCC pVHL-Low, ALK5-FL, ALK5-ICD, pSMAD2/3, and PAI-1 were significantly related with tumor stage, size, and survival. In ccRCC pVHL-High, the expression of PAI-1 was associated with stage and survival. In-vitro studies revealed that pVHL interacted with ALK5 to downregulate its expression through K48-linked poly-ubiquitination and proteasomal degradation, thus negatively controlling TGF-β induced cancer cell invasiveness. The pVHL status controls the ALK5 and can thereby regulate the TGF-β pathway, aggressiveness of tumors, and survival of the ccRCC and non-ccRCC patients.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- 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
- ccRCC
- non-ccRCC
- ALK5
- pVHL
- TGF-β signaling
- molecular cell biology
- molekylär cellbiologi
- Cancer Epidemiology
- cancerepidemiologi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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