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-fl...

Full description

Saved in:
Bibliographic Details
Published in:Cancer letters 2009-06, Vol.279 (1), p.39-46
Main Authors: Costantino, Eleonora, Maddalena, Francesca, Calise, Serena, Piscazzi, Annamaria, Tirino, Virginia, Fersini, Alberto, Ambrosi, Antonio, Neri, Vincenzo, Esposito, Franca, Landriscina, Matteo
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Bone cancer
Camptothecin - analogs & derivatives
Camptothecin - pharmacology
Cancer therapies
Carcinoma - genetics
Carcinoma - metabolism
Carcinoma - pathology
Chemoresistance
Chemotherapy
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Deoxyribonucleic acid
DNA
Dose-Response Relationship, Drug
Drug resistance
Drug Resistance, Multiple - genetics
Drug Resistance, Neoplasm - genetics
Female
Fluorouracil - pharmacology
Gene Expression Regulation, Neoplastic
Genotype
Hematology, Oncology and Palliative Medicine
HSP90 Heat-Shock Proteins - antagonists & inhibitors
HSP90 Heat-Shock Proteins - genetics
HSP90 Heat-Shock Proteins - metabolism
HT29 Cells
Humans
Male
Middle Aged
Mitochondria
Mitochondria - drug effects
Mitochondria - metabolism
Mitochondria - pathology
Organoplatinum Compounds - pharmacology
Oxidative stress
Peptide Fragments - pharmacology
Phenotype
Proteins
RNA, Messenger - metabolism
Transfection
TRAP1
Up-Regulation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2009.01.018