التفاصيل البيبلوغرافية
| العنوان: |
NFκ B1 is a suppressor of neutrophil-driven hepatocellular carcinoma |
| المؤلفون: |
Wilson, CL, Jurk, D, Fullard, N, Banks, P, Page, A, Luli, S, Elsharkawy, AM, Gieling, RG, Chakraborty, JB, Fox, C, Richardson, C, Callaghan, K, Blair, GE, Fox, N, Lagnado, A, Passos, JF, Moore, AJ, Smith, GR, Tiniakos, DG, Mann, J, Oakley, F, Mann, DA |
| بيانات النشر: |
Nature Publishing Group, 2015. |
| سنة النشر: |
2015 |
| مصطلحات موضوعية: |
digestive system diseases |
| الوصف: |
Hepatocellular carcinoma (HCC) develops on the background of chronic hepatitis. Leukocytes found within the HCC microenvironment are implicated as regulators of tumour growth. We show that diethylnitrosamine (DEN)-induced murine HCC is attenuated by antibody-mediated depletion of hepatic neutrophils, the latter stimulating hepatocellular ROS and telomere DNA damage. We additionally report a previously unappreciated tumour suppressor function for hepatocellular nfkb1 operating via p50:p50 dimers and the co-repressor HDAC1. These anti-inflammatory proteins combine to transcriptionally repress hepatic expression of a S100A8/9, CXCL1 and CXCL2 neutrophil chemokine network. Loss of nfkb1 promotes ageing-associated chronic liver disease (CLD), characterized by steatosis, neutrophillia, fibrosis, hepatocyte telomere damage and HCC. Nfkb1 S340A/S340A mice carrying a mutation designed to selectively disrupt p50:p50:HDAC1 complexes are more susceptible to HCC; by contrast, mice lacking S100A9 express reduced neutrophil chemokines and are protected from HCC. Inhibiting neutrophil accumulation in CLD or targeting their tumour-promoting activities may offer therapeutic opportunities in HCC. |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| تدمد: |
2041-1723 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=core_ac_uk__::d3c80001d581a0aeaaf652b615b63338 |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.core.ac.uk....d3c80001d581a0aeaaf652b615b63338 |
| قاعدة البيانات: |
OpenAIRE |