TRAP1 revisited: Novel localizations and functions of a ‘next-generation’ biomarker (Review)

Amoroso,Maria Rosaria; Matassa,Danilo  Swann; Sisinni,Lorenza; Lettini,Giacomo; Landriscina,Matteo; Esposito,Franca

doi:10.3892/ijo.2014.2530

TRAP1 revisited: Novel localizations and functions of a ‘next-generation’ biomarker (Review)

Authors:
- Maria Rosaria Amoroso
- Danilo Swann Matassa
- Lorenza Sisinni
- Giacomo Lettini
- Matteo Landriscina
- Franca Esposito
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Affiliations: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy, Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy, Laboratory of Pre-Clinical and Translational Research, IRCCS, Referral Cancer Centre of Basilicata, Rionero in Vulture, PZ, Italy, Clinical Oncology Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
Published online on: June 27, 2014 https://doi.org/10.3892/ijo.2014.2530
Pages: 969-977

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Abstract

In the last decade, the identification and characterization of novel molecular mechanisms and pathways involving the heat shock protein TRAP1/HSP75 in cancers and other diseases enhanced the scientific interest. Recent reports have shown that TRAP1 stays at the crossroad of multiple crucial processes in the onset of neoplastic transformation. In fact, TRAP1: i) contributes to the tumor's switch to aerobic glycolysis through the inhibition of succinate dehydrogenase, the complex II of the mitochondrial respiratory chain; ii) is part of a pro-survival signaling pathway aimed at evading the toxic effects of oxidants and anticancer drugs and protects mitochondria against damaging stimuli via a decrease of ROS generation; iii) controls protein homeostasis through a direct involvement in the regulation of protein synthesis and protein co-translational degradation. Therefore, TRAP1 seems to be a central regulatory protein with balancing functions at the intersection of different metabolic processes during the neoplastic transformation. For this reason, it can be considered at the same time an attractive target for the development of novel anticancer strategies and a promising study model to understand the biology of tumor cells at a systemic level. This review summarizes the most recent advances in TRAP1 biology and proposes a new comprehensive view of its functions.

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