Stress-Adaptive Response in Ovarian Cancer Drug Resistance: Role of TRAP1 in Oxidative Metabolism-Driven Inflammation

Maria Rosaria Amoroso, Danilo Swann Matassa, Ilenia Agliarulo, Rosario Avolio, Francesca Maddalena, Valentina Condelli, Matteo Landriscina, Franca Esposito

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Metabolic reprogramming is one of the most frequent stress-adaptive response of cancer cells to survive environmental changes and meet increasing nutrient requirements during their growth. These modifications involve cellular bioenergetics and cross talk with surrounding microenvironment, in a dynamic network that connect different molecular processes, such as energy production, inflammatory response, and drug resistance. Even though the Warburg effect has long been considered the main metabolic feature of cancer cells, recent reports identify mitochondrial oxidative metabolism as a driving force for tumor growth in an increasing number of cellular contexts. In recent years, oxidative phosphorylation has been linked to a remodeling of inflammatory response due to autocrine or paracrine secretion of interleukines that, in turn, induces a regulation of gene expression involving, among others, molecules responsible for the onset of drug resistance. This process is especially relevant in ovarian cancer, characterized by low survival, high frequency of disease relapse and chemoresistance. Recently, the molecular chaperone TRAP1 (tumor necrosis factor-associated protein 1) has been identified as a key junction molecule in these processes in ovarian cancer: in fact, TRAP1 mediates a metabolic switch toward oxidative phosphorylation that, in turn, triggers cytokines secretion, with consequent gene expression remodeling, finally leading to cisplatin resistance and epithelial-to-mesenchymal transition in ovarian cancer models. This review summarizes how metabolism, chemoresistance, inflammation, and epithelial-to-mesenchymal transition are strictly interconnected, and how TRAP1 stays at the crossroads of these processes, thus shedding new lights on molecular networks at the basis of ovarian cancer.

Original languageEnglish
Title of host publicationAdvances in Protein Chemistry and Structural Biology
PublisherAcademic Press Inc.
Pages163-198
Number of pages36
Volume108
DOIs
Publication statusPublished - Jan 1 2017

Publication series

NameAdvances in Protein Chemistry and Structural Biology
Volume108
ISSN (Print)1876-1623

Keywords

  • Chemoresistance
  • Cisplatin resistance
  • Combinatorial therapy
  • Epithelial-to-mesenchymal transition
  • Inflammation
  • Metabolic rewiring
  • Ovarian cancer
  • Oxidative phosphorylation
  • Stress-adaptive responses
  • TRAP1

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry

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