Fiche publication
Date publication
octobre 2011
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GARRIDO Carmen
,
Dr GOBBO Jessica
,
Dr JEGO Gaëtan
Tous les auteurs :
Dorard C, de Thonel A, Collura A, Marisa L, Svrcek M, Lagrange A, Jego G, Wanherdrick K, Joly AL, Buhard O, Gobbo J, Penard-Lacronique V, Zouali H, Tubacher E, Kirzin S, Selves J, Milano G, Etienne-Grimaldi MC, Bengrine-Lefevre L, Louvet C, Tournigand C, Lefevre JH, Parc Y, Tiret E, Flejou JF, Gaub MP, Garrido C, Duval A
Lien Pubmed
Résumé
Heat shock proteins (HSPs) are necessary for cancer cell survival. We identified a mutant of HSP110 (HSP110DeltaE9) in colorectal cancer showing microsatellite instability (MSI CRC), generated from an aberrantly spliced mRNA and lacking the HSP110 substrate-binding domain. This mutant was expressed at variable levels in almost all MSI CRC cell lines and primary tumors tested. HSP110DeltaE9 impaired both the normal cellular localization of HSP110 and its interaction with other HSPs, thus abrogating the chaperone activity and antiapoptotic function of HSP110 in a dominant-negative manner. HSP110DeltaE9 overexpression caused the sensitization of cells to anticancer agents such as oxaliplatin and 5-fluorouracil, which are routinely prescribed in the adjuvant treatment of people with CRC. The survival and response to chemotherapy of subjects with MSI CRCs was associated with the tumor expression level of HSP110DeltaE9. HSP110 may thus constitute a major determinant for both prognosis and treatment response in CRC.
Référence
Nat Med. 2011 Sep 25;17(10):1283-9
