VEGFC acts as a double-edged sword in renal cell carcinoma aggressiveness

Theranostics
Papa Diogop NdiayeGilles Pages

Abstract

Hypoxic zones are common features of metastatic tumors. Due to inactivation of the von Hippel-Lindau gene (VHL), renal cell carcinomas (RCC) show constitutive stabilization of the alpha subunit of the hypoxia-inducible factor (HIF). Thus, RCC represents a model of chronic hypoxia. Development of the lymphatic network is dependent on vascular endothelial growth factor C (VEGFC) and lies at the front line of metastatic spreading. Here, we addressed the role of VEGFC in RCC aggressiveness and the regulation of its expression in hypoxia. Methods: Transcriptional and post transcriptional regulation of VEGFC expression was evaluated by qPCR and with reporter genes. The involvement of HIF was evaluated using a siRNA approach. Experimental RCC were performed with immuno-competent/deficient mice using human and mouse cells knocked-out for the VEGFC gene by a CRISPR/Cas9 method. The VEGFC axis was analyzed with an online available data base (TCGA) and using an independent cohort of patients. Results: Hypoxia induced VEGFC protein expression but down-regulated VEGFC gene transcription and mRNA stability. Increased proliferation, migration, over-activation of the AKT signaling pathway and enhanced expression of mesenchymal markers characte...Continue Reading

Citations

Aug 9, 2020·Frontiers in Cell and Developmental Biology·Aurore Dumond, Gilles Pagès
Aug 11, 2020·Frontiers in Cell and Developmental Biology·Christopher Montemagno, Gilles Pagès
Oct 18, 2020·Communications Biology·Manon Penco-CampilloGilles Pagès
Feb 28, 2021·Cell Death & Disease·Xingting BaoHong Zhang

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Methods Mentioned

BETA
PCR
flow cytometry
xenograft
ELISA
transfections
transfection
ChIP
FCS
gene knock-out

Software Mentioned

R
Prism
Diva
GraphPad

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