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Thermogenic protein UCP1 and UCP3 expression in non- small cell lung cancer： relation with glycolysis and anaerobic metabolism

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Cancer Biology & Medicine 2017年第4期14卷 396-404页

作者： Alexandra Giatromanolaki Konstantina Balaska Dimitra Kalamida christos kakouratos Efthimios Sivridis Michael I. Koukourakis Department of Pathology Department of Radiotherapy/Oncology Democritus University of Thrace University Hospital ofAlexandroupolis Alexandroupolis 68100 Greece

Uncoupling protein 1(UCP1)is a proton transporter/channel residing on the inner mitochondrial membrane and is involved in cellular heat *** immunohistochemistry,we investigated the expression of UCP1 and UCP3 in a series of 98 patients with non-small cell lung cancer(NSCLC)treated with *** patterns were correlated with histopathological variables,prognosis,and the expression of enzymes/proteins related to cell *** epithelium did not express UCP1 or UCP3,while alveolar cells strongly expressed *** tumors,strong expression of UCP1 and UCP3 was recorded in43/98(43.8%)and 27/98(27.6%)cases,***1 was significantly associated with squamous cell histology(P=0.05),whilst UCP3 was more frequently overexpressed in large cell carcinomas(P=0.08),and was inversely related to necrosis(P=0.009).In linear regression analysis,UCP1 was directly related to markers of glycolysis[hexokinase(HXKII)and phosphofructokinase(PFK1)]and anaerobic glucose metabolism[pyruvate dehydrogenase kinase(PDK1)and lactate dehydrogenase(LDH5)].UCP3 was directly linked with a glucose transporter(GLUT2),monocarboxylate transporter(MCT2),glycolysis markers(PFK1 and aldolase),and with the phosphorylation of pyruvate dehydrogenase(p PDH).Kaplan-Meier survival analysis showed that UCP3 was significantly related to poor prognosis in squamous cell carcinomas(P=0.04).UCP1 and UCP3 are overexpressed in a large subgroup of non-small cell lung tumors and their expression coincides with increased glucose absorption,intensified glycolysis,and anaerobic glucose *** UCPs are targets for therapeutic interventions in lung cancer is a hypothesis that demands further investigation.

关键词： Lung cancer thermogenesis UCP1 UCP3 glycolysis anaerobic metabolism

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