TY - JOUR
T1 - Oxidative phosphorylation induces de novo expression of the MHC class I in tumor cells through the ERK5 pathway
AU - Charni, Seyma
AU - De Bettignies, Geoffroy
AU - Rathore, Moeez G.
AU - Aguilo, Juan I.
AU - Van Den Elsen, Peter J.
AU - Haouzi, Delphine
AU - Hipskind, Robert A.
AU - Enriquez, José Antonio
AU - Sanchez-Beato, Margarita
AU - Pardo, Julián
AU - Anel, Alberto
AU - Villalba, Martin
PY - 2010/9/15
Y1 - 2010/9/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78649829433&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78649829433&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1001250
DO - 10.4049/jimmunol.1001250
M3 - Article
C2 - 20729331
AN - SCOPUS:78649829433
SN - 0022-1767
VL - 185
SP - 3498
EP - 3503
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -