TRAP1, a novel mitochondrial chaperone responsible for multi-drug resistance and protection from apoptotis in human colorectal carcinoma cells

Eleonora Costantino; Francesca Maddalena; Serena Calise; Annamaria Piscazzi; Virginia Tirino; Alberto Fersini; Antonio Ambrosi; Vincenzo Neri; Franca Esposito; Matteo Landriscina

doi:10.1016/j.canlet.2009.01.018

TRAP1, a novel mitochondrial chaperone responsible for multi-drug resistance and protection from apoptotis in human colorectal carcinoma cells

Eleonora Costantino, Francesca Maddalena, Serena Calise, Annamaria Piscazzi, Virginia Tirino, Alberto Fersini, Antonio Ambrosi, Vincenzo Neri, Franca Esposito, Matteo Landriscina

IRCCS Centro di Riferimento Oncologico della Basilicata (CROB)

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	39-46
Number of pages	8
Journal	Cancer Letters
Volume	279
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2009.01.018
Publication status	Published - Jun 28 2009

Keywords

Apoptosis
Chemoresistance
Chemotherapy
Colorectal carcinoma
Oxidative stress
TRAP1

ASJC Scopus subject areas

Cancer Research
Oncology

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TRAP1, a novel mitochondrial chaperone responsible for multi-drug resistance and protection from apoptotis in human colorectal carcinoma cells. / Costantino, Eleonora; Maddalena, Francesca; Calise, Serena; Piscazzi, Annamaria; Tirino, Virginia; Fersini, Alberto; Ambrosi, Antonio; Neri, Vincenzo; Esposito, Franca; Landriscina, Matteo.

In: Cancer Letters, Vol. 279, No. 1, 28.06.2009, p. 39-46.

Research output: Contribution to journal › Article › peer-review

Costantino, Eleonora ; Maddalena, Francesca ; Calise, Serena ; Piscazzi, Annamaria ; Tirino, Virginia ; Fersini, Alberto ; Ambrosi, Antonio ; Neri, Vincenzo ; Esposito, Franca ; Landriscina, Matteo. / TRAP1, a novel mitochondrial chaperone responsible for multi-drug resistance and protection from apoptotis in human colorectal carcinoma cells. In: Cancer Letters. 2009 ; Vol. 279, No. 1. pp. 39-46.

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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.",

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AU - Fersini, Alberto

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