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

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)39-46
Number of pages8
JournalCancer Letters
Volume279
Issue number1
DOIs
Publication statusPublished - Jun 28 2009

Keywords

  • Apoptosis
  • Chemoresistance
  • Chemotherapy
  • Colorectal carcinoma
  • Oxidative stress
  • TRAP1

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Costantino, E., Maddalena, F., Calise, S., Piscazzi, A., Tirino, V., Fersini, A., Ambrosi, A., Neri, V., Esposito, F., & Landriscina, M. (2009). TRAP1, a novel mitochondrial chaperone responsible for multi-drug resistance and protection from apoptotis in human colorectal carcinoma cells. Cancer Letters, 279(1), 39-46. https://doi.org/10.1016/j.canlet.2009.01.018