[en] Heat shock protein 110 (HSP110) is induced by different stresses and, through its anti-apoptotic and chaperoning properties, helps cells survive these adverse situations. In colon cancers, HSP110 is abnormally abundant. We have recently shown that colorectal cancer patients with microsatellite instability (MSI) had an improved response to chemotherapy because they harbor an HSP110inactivating mutation (HSP110DE9). In this work, we used patient biopsies, human colorectal cancer cells grown in vitro and in vivo (xenografts), and intestinal crypts to demonstrate that HSP110 is also involved in colon cancer growth. We showed that HSP110 induces colon cancer cell proliferation and that this effect is associated with STAT3 activation, specifically an increase in STAT3 phosphorylation, nuclear translocation and transcription factor activity. STAT3 inhibition blocks the proliferative effect of HSP110. From a molecular standpoint, we demonstrated that HSP110 directly binds to STAT3, thereby facilitating its phosphorylation by JAK2. Finally, we showed a correlation between HSP110 expression and STAT3 phosphorylation in colon cancer patient samples. Thus, the expression of HSP110 in colon cancer contributes to STAT3-dependent tumor growth and the frequent inactivating mutation of this chaperone is probably an important event underlying the improved prognosis in colon cancer displaying MSI.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Berthenet, K; UMR866, Faculté des Sciences de Santé, INSERM, Université de Bourgogne Franche-Comté, Dijon, France ; INSERM ; Equipe Labellisée Ligue Nationale Contre le Cancer, Dijon, France
Dem Bokhari, A; UMR 938, INSERM, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Paris, France ; Université Pierre et Marie Curie-Paris 6, Paris, France
Lagrange, A; UMR 938, INSERM, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Paris, France ; Université Pierre et Marie Curie-Paris 6, Paris, France
Marcion, Guillaume ; Université de Liège - ULiège > GIGA > GIGA I3 - Hematology ; UMR866, Faculté des Sciences de Santé, INSERM, Université de Bourgogne Franche-Comté, Dijon, France ; INSERM ; Equipe Labellisée Ligue Nationale Contre le Cancer, Dijon, France
Boudesco, C; UMR866, Faculté des Sciences de Santé, INSERM, Université de Bourgogne Franche-Comté, Dijon, France ; INSERM ; Equipe Labellisée Ligue Nationale Contre le Cancer, Dijon, France
Causse, S ; UMR866, Faculté des Sciences de Santé, INSERM, Université de Bourgogne Franche-Comté, Dijon, France ; INSERM ; Equipe Labellisée Ligue Nationale Contre le Cancer, Dijon, France
De Thonel, A; UMR7216 Epigenetics and Cell Fate, CNRS, Paris, France
Svrcek, M; UMR 938, INSERM, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Paris, France ; Université Pierre et Marie Curie-Paris 6, Paris, France
Goloudina, A R; UMR866, Faculté des Sciences de Santé, INSERM, Université de Bourgogne Franche-Comté, Dijon, France ; INSERM ; Equipe Labellisée Ligue Nationale Contre le Cancer, Dijon, France
Dumont, S; AP-HP, Hôpital St Antoine, Paris, France
Hammann, A; UMR866, Faculté des Sciences de Santé, INSERM, Université de Bourgogne Franche-Comté, Dijon, France ; INSERM ; Equipe Labellisée Ligue Nationale Contre le Cancer, Dijon, France
Biard, D S; UMR866, Faculté des Sciences de Santé, INSERM, Université de Bourgogne Franche-Comté, Dijon, France ; Centre d'Etude Atomique, Paris, France
Seigneuric, R; UMR866, Faculté des Sciences de Santé, INSERM, Université de Bourgogne Franche-Comté, Dijon, France ; INSERM ; Equipe Labellisée Ligue Nationale Contre le Cancer, Dijon, France
Duval, A ; INSERM ; Equipe Labellisée Ligue Nationale Contre le Cancer, Dijon, France ; UMR 938, INSERM, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Paris, France ; Université Pierre et Marie Curie-Paris 6, Paris, France
Collura, A; UMR 938, INSERM, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Paris, France ; Université Pierre et Marie Curie-Paris 6, Paris, France
Jego, G; UMR866, Faculté des Sciences de Santé, INSERM, Université de Bourgogne Franche-Comté, Dijon, France ; INSERM ; Equipe Labellisée Ligue Nationale Contre le Cancer, Dijon, France
Garrido, C; UMR866, Faculté des Sciences de Santé, INSERM, Université de Bourgogne Franche-Comté, Dijon, France ; INSERM ; Equipe Labellisée Ligue Nationale Contre le Cancer, Dijon, France ; CGFL, Dijon, France
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