title: TRAP1, a novel mitochondrial chaperone responsible for multi-drug resistance and protection from apoptotis in human colorectal carcinoma cells.
abstract: TRAP1 is a component of a pro-survival mitochondrial pathway up-regulated in tumor cells. The evaluation of TRAP1 expression in 26 human colorectal carcinomas showed up-regulation in 17/26 tumors. Accordingly, TRAP1 levels were increased in HT-29 colorectal carcinoma cells resistant to 5-fluorouracil, oxaliplatin and irinotecan. Thus, we investigated the role of TRAP1 in multi-drug resistance in human colorectal cancer. Interestingly, TRAP1 overexpression leads to 5-fluorouracil-, oxaliplatin- and irinotecan-resistant phenotypes in different neoplastic cells. Conversely, the inhibition of TRAP1 activity by TRAP1 ATPase antagonist, shepherdin, increased the sensitivity to oxaliplatin and irinotecan in colorectal carcinoma cells resistant to the single agents. These results suggest that the increased expression of TRAP1 could be part of a pro-survival pathway responsible for multi-drug resistance.
authors.affiliation: Clinical Oncology Unit, Department of Medical Sciences, University of Foggia, Viale Pinto 1, 71100 Foggia, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Costantino
authors.forename: Francesca
authors.initials: F
authors.lastname: Maddalena
authors.forename: Serena
authors.initials: S
authors.lastname: Calise
authors.forename: Annamaria
authors.initials: A
authors.lastname: Piscazzi
authors.forename: Virginia
authors.initials: V
authors.lastname: Tirino
authors.forename: Alberto
authors.initials: A
authors.lastname: Fersini
authors.forename: Antonio
authors.initials: A
authors.lastname: Ambrosi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Neri
authors.forename: Franca
authors.initials: F
authors.lastname: Esposito
authors.forename: Matteo
authors.initials: M
authors.lastname: Landriscina
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D010446:Peptide Fragments / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D009944:Organoplatinum Compounds; D010446:Peptide Fragments; D012333:RNA, Messenger; C092306:TRAP1 protein, human; C503112:shepherdin; D000077150:Oxaliplatin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin