喂,警察叔叔么?HSP110在促进肠癌生长!
  • HSP110由不同应激诱导,通过抗凋亡和伴侣特性帮助细胞在不利情况下存活;
  • HSP110在结肠癌中高表达,具有MSI的结直肠癌患者具有其失活突变,对化疗反应有改善;
  • HSP110通过活化STAT3诱导结肠癌细胞增殖,尤其升高STAT3磷酸化、核转运和转录因子活性,抑制STAT3阻断HSP110的增殖作用;
  • HSP110直接与STAT3结合促进其磷酸化,HSP110表达和STAT3磷酸化相关;
  • HSP110在结肠癌中有助于STAT3依赖性肿瘤生长,其失活突变标志着预后改善。
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Oncogene [IF:7.971]

HSP110 promotes colorectal cancer growth through STAT3 activation

HSP110通过激活STAT3促进结直肠癌生长

10.1038/onc.2016.403

2017-04-20, Article

Abstract & Authors:展开

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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 HSP110-inactivating 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.

First Authors:
K Berthenet,A'dem Bokhari,A Collura,G Jego,C Garrido

Correspondence Authors:
G Jego,C Garrido

All Authors:
K Berthenet,A'dem Bokhari,A Lagrange,G Marcion,C Boudesco,S Causse,A De Thonel,M Svrcek,A R Goloudina,S Dumont,A Hammann,D S Biard,O N Demidov,R Seigneuric,A Duval,A Collura,G Jego,C Garrido

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