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However, its expression in renal carcinomas inversely correlates with tumor malignancy. Our experiments in clear cell renal cell carcinoma (ccRCC) cell lines demonstrated that von Hippel Lindau (VHL) loss, hypoxia, or PHD (for prolyl hydroxylase domain\u2013containing proteins) inactivation decreased VCAM-1 levels through a transcriptional mechanism that was independent of the hypoxia-inducible factor and dependent on the nuclear factor \u03baB signaling pathway. Conversely, VHL expression leads to high VCAM-1 levels in ccRCC, which in turn leads to better outcomes, possibly by favoring antitumor immunity through VCAM-1 interaction with the \u03b14\u03b21 integrin expressed in immune cells. Remarkably, in ccRCC human samples with VHL nonmissense mutations, we observed a negative correlation between VCAM-1 levels and ccRCC stage, microvascular invasion, and symptom presentation, pointing out the clinical value of VCAM-1 levels as a marker of ccRCC progression.<\/jats:p>","DOI":"10.1083\/jcb.201608024","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T11:20:19Z","timestamp":1487935219000},"page":"835-847","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["VHL promotes immune response against renal cell carcinoma via NF-\u03baB\u2013dependent regulation of VCAM-1"],"prefix":"10.1083","volume":"216","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9690-145X","authenticated-orcid":true,"given":"David","family":"Labrousse-Arias","sequence":"first","affiliation":[{"name":"Department of Medicine, Instituto de Investigaci\u00f3n Sanitaria Princesa, School of Medicine, 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