Oxidative phosphorylation induces de novo expression of the MHC class I in tumor cells through the ERK5 pathway

Seyma Charni, Geoffroy De Bettignies, Moeez G. Rathore, Juan I. Aguilo, Peter J. Van Den Elsen, Delphine Haouzi, Robert A. Hipskind, José Antonio Enriquez, Margarita Sanchez-Beato, Julián Pardo, Alberto Anel, Martin Villalba

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Most cancer cells use anaerobic-like glycolysis to generate energy instead of oxidative phosphorylation. They also avoid recognition by CTLs, which occurs primarily through decreasing the level of MHC class I (MHC-I) at the cell surface. We find that the two phenomena are linked; culture conditions that force respiration in leukemia cells upregulate MHC-I transcription and protein levels at the cell surface, whereas these decrease in cells forced to perform fermentation as well as in leukemia cells lacking a functional mitochondrial respiratory chain. Forced respiration leads to increased expression of the MAPK ERK5, which activates MHC-I gene promoters, and ERK5 accumulation in mitochondria. Respiration-induced MHC-I upregulation is reversed upon short hairpin RNA-mediated ERK5 downregulation and by inactive mutants of ERK5. Moreover, short hairpin RNA for ERK5 leukemia cells do not tolerate forced respiration. Thus, the expression of ERK5 and MHC-I is linked to cell metabolism and notably diminished by the metabolic adaptations found in tumor cells.

Original languageEnglish (US)
Pages (from-to)3498-3503
Number of pages6
JournalJournal of Immunology
Volume185
Issue number6
DOIs
StatePublished - Sep 15 2010

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