The pVHL172 isoform is not a tumor suppressor and up-regulates a subset of pro-tumorigenic genes including TGFB1 and MMP13

Oncotarget
P HascoetY Arlot-Bonnemains

Abstract

The von Hippel-Lindau (VHL) tumor suppressor gene is often deleted or mutated in ccRCC (clear cell renal cell carcinoma) producing a non-functional protein. The gene encodes two mRNA, and three protein isoforms (pVHL213, pVHL160 and pVHL172). The pVHL protein is part of an E3 ligase complex involved in the ubiquitination and proteasomal degradation of different proteins, particularly hypoxia inducible factors (HIF) that drive the transcription of genes involved in the regulation of cell proliferation, angiogenesis or extracellular matrix remodelling. Other non-canonical (HIF-independent) pVHL functions have been described. A recent work reported the expression of the uncharacterized protein isoform pVHL172 which is translated from the variant 2 by alternative splicing of the exon 2. This splice variant is sometimes enriched in the ccRCCs and the protein has been identified in the respective samples of ccRCCs and different renal cell lines. Functional studies on pVHL have only concerned the pVHL213 and pVHL160 isoforms, but no function was assigned to pVHL172. Here we show that pVHL172 stable expression in renal cancer cells does not regulate the level of HIF, exacerbates tumorigenicity when 786-O-pVHL172 cells were xenografted ...Continue Reading

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Citations

Apr 5, 2019·The Journal of Clinical Endocrinology and Metabolism·Shahida K FloresPatricia L M Dahia
Sep 29, 2020·Scientific Reports·Antonella FalconieriSilvio C E Tosatto
Oct 29, 2020·Journal of Experimental & Clinical Cancer Research : CR·Tiansheng LiYongguang Tao
Apr 7, 2021·Briefings in Bioinformatics·Yangjun ZhangHua Xu

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Methods Mentioned

BETA
xenograft
xenografting
transfection
gelatinase assay
zymography
PCR

Software Mentioned

Image J
SimplePCI6
studio
R
view2
ImageJ
ZEN
NDP

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