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325270 occurrences (No.61 in the rank) during 5 years in the PubMed. [no cache] 500 found
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325270 occurrences (No.61 in the rank) during 5 years in the PubMed. [no cache] 500 found
| 269) This finding may provide insight into intricate PC functions that seem to be independent from their substrate-processing activity. |
| PMID:24436242 DOI:10.1002/mc.22131 |
| 2015 Molecular carcinogenesis |
| * Regulation of HIF-1 alpha by the proprotein convertases furin and PC7 in human squamous carcinoma cells. |
| - Proprotein convertases (PC), a family of serine proteases, process cancer-related substrates such as growth factors, growth factor receptors, cell adhesion molecules, metalloproteinases, etc. HIF-1α is a major transcription factor involved in tumorigenesis by sensing intratumoral hypoxia. Furin (PCSK3) is one of the numerous target genes regulated by HIF-1α transactivation and its distribution into endosomal compartments and onto the cell surface can be triggered by hypoxia via HIF-1α. siRNAs to knockdown PCs were transfected into cells alone or in combination with different drug treatments. Protein and RNA expression levels were analyzed by Western blotting or RT-PCR, respectively. PC7 (PCSK7) and furin siRNAs upregulated HIF-1α protein under normoxic condition to a level similar to that obtained by cobalt chloride treatment, eventually leading to activation of VEGF-A synthesis in two human head and neck squamous cell carcinoma cell lines. The unchanged levels of HIF-1α mRNA expression under siRNA treatment and the additive HIF-1α induction of PC siRNAs and either cobalt chloride or the 26S ribosome inhibitor, MG-132, suggested a post-transcriptional PC-mediated regulation. Furthermore, cycloheximide chase showed that PC7/furin siRNA regulation occurred at the level of HIF-1α translation. A specific IGF-1R signaling inhibitor was able to attenuate the PC siRNA induction of HIF-1α, suggesting the involvement of the IGF-1R pathway. Thus, the data show that PCs regulate HIF-1α. Furin and PC7 siRNAs induced HIF-1α protein by increasing its translation, resulting in upregulation of VEGF-A. This finding may provide insight into intricate PC functions that seem to be independent from their substrate-processing activity. |
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(34)2 effective |
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(38)2 greater |
| (6)13 new |
(17)4 insights |
(28)2 accurate |
(39)2 methodological |
| (7)8 more |
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| (8)7 rather |
(19)4 us |
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(20)4 valuable |
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(33)2 clinically |
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--- WordNet output for provide ---