Open AccessTRAP1‐dependent regulation of p70S6K is involved in the attenuation of protein synthesis and cell migration: Relevance in human colorectal tumors
Author(s) -
Matassa Danilo Swann,
Agliarulo Ilenia,
Amoroso Maria Rosaria,
Maddalena Francesca,
Sepe Leandra,
Ferrari Maria Carla,
Sagar Vinay,
D'Amico Silvia,
Loreni Fabrizio,
Paolella Giovanni,
Landriscina Matteo,
Esposito Franca
Publication year - 2014
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2014.06.003
Subject(s) - cdc37 , microbiology and biotechnology , translational regulation , signal transduction , biology , kinase , chaperone (clinical) , phosphorylation , gene silencing , translation (biology) , messenger rna , mapk/erk pathway , medicine , genetics , gene , extracellular signal regulated kinases , pathology
TNF receptor‐associated protein 1 (TRAP1) is an HSP90 chaperone involved in stress protection and apoptosis in mitochondrial and extramitochondrial compartments. Remarkably, aberrant deregulation of TRAP1 function has been observed in several cancer types with potential new opportunities for therapeutic intervention in humans. Although previous studies by our group identified novel roles of TRAP1 in quality control of mitochondria‐destined proteins through the attenuation of protein synthesis, molecular mechanisms are still largely unknown. To shed further light on the signaling pathways regulated by TRAP1 in the attenuation of protein synthesis, this study demonstrates that the entire pathway of cap‐mediated translation is activated in cells following TRAP1 interference: consistently, expression and consequent phosphorylation of p70S6K and RSK1, two translation activating kinases, are increased upon TRAP1 silencing. Furthermore, we show that these regulatory functions affect the response to translational stress and cell migration in wound healing assays, processes involving both kinases. Notably, the regulatory mechanisms controlled by TRAP1 are conserved in colorectal cancer tissues, since an inverse correlation between TRAP1 and p70S6K expression is found in tumor tissues, thereby supporting the relevant role of TRAP1 translational regulation in vivo. Taken as a whole, these new findings candidate TRAP1 network for new anti‐cancer strategies aimed at targeting the translational/quality control machinery of tumor cells.