Expression of a mutant HSP110 sensitizes colorectal cancer cells to chemotherapy and improves disease prognosis | Zendy

Coralie Dorard | Zendy; Aurélie de Thonel | Zendy; Ada Collura | Zendy; Laëtitia Marisa | Zendy; Magali Svrcek | Zendy; Anaïs Lagrange | Zendy; Gaëtan Jégo | Zendy; Kristell Wanherdrick | Zendy; A Joly | Zendy; Olivier Buhard | Zendy; Jessica Gobbo | Zendy; Virginie Penard-Lacronique | Zendy; Habib Zouali | Zendy; Emmanuel Tubacher | Zendy; Sylvain Kirzin | Zendy; Janick Sèlves | Zendy; Gérard Milano | Zendy; Marie-Christine Étienne-Grimaldi | Zendy; Léïla Bengrine-Lefèvre | Zendy; Christophe Louvet | Zendy; Christophe Tournigand | Zendy; Jérémie H. Lefèvre | Zendy; Yann Parc | Zendy; Emmanuel Tiret | Zendy; Jean–François Fléjou | Zendy; MariePierre Gaub | Zendy; Alex Duval | Zendy

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Expression of a mutant HSP110 sensitizes colorectal cancer cells to chemotherapy and improves disease prognosis

Author(s) -

Coralie Dorard,

Aurélie de Thonel,

Ada Collura,

Laëtitia Marisa,

Magali Svrcek,

Anaïs Lagrange,

Gaëtan Jégo,

Kristell Wanherdrick,

A Joly,

Olivier Buhard,

Jessica Gobbo,

Virginie Penard-Lacronique,

Habib Zouali,

Emmanuel Tubacher,

Sylvain Kirzin,

Janick Sèlves,

Gérard Milano,

Marie-Christine Étienne-Grimaldi,

Léïla Bengrine-Lefèvre,

Christophe Louvet,

Christophe Tournigand,

Jérémie H. Lefèvre,

Yann Parc,

Emmanuel Tiret,

Jean–François Fléjou,

MariePierre Gaub,

Alex Duval

Publication year - 2011

Publication title -

nature medicine

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 19.536

H-Index - 547

eISSN - 1546-170X

pISSN - 1078-8956

DOI - 10.1038/nm.2457

Subject(s) - oxaliplatin , colorectal cancer , microsatellite instability , cancer research , heat shock protein , biology , chaperone (clinical) , mutant , cancer , medicine , immunology , gene , pathology , genetics , allele , microsatellite

Heat shock proteins (HSPs) are necessary for cancer cell survival. We identified a mutant of HSP110 (HSP110ΔE9) 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. HSP110ΔE9 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. HSP110ΔE9 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 HSP110ΔE9. HSP110 may thus constitute a major determinant for both prognosis and treatment response in CRC.

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