TY - JOUR
T1 - TRAP1, a novel mitochondrial chaperone responsible for multi-drug resistance and protection from apoptotis in human colorectal carcinoma cells
AU - Costantino, Eleonora
AU - Maddalena, Francesca
AU - Calise, Serena
AU - Piscazzi, Annamaria
AU - Tirino, Virginia
AU - Fersini, Alberto
AU - Ambrosi, Antonio
AU - Neri, Vincenzo
AU - Esposito, Franca
AU - Landriscina, Matteo
PY - 2009/6/28
Y1 - 2009/6/28
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Chemoresistance
KW - Chemotherapy
KW - Colorectal carcinoma
KW - Oxidative stress
KW - TRAP1
UR - http://www.scopus.com/inward/record.url?scp=67349088746&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349088746&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2009.01.018
DO - 10.1016/j.canlet.2009.01.018
M3 - Article
C2 - 19217207
AN - SCOPUS:67349088746
VL - 279
SP - 39
EP - 46
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 1
ER -