In this study, we investigated the role of cancer-associated fibroblasts (CAFs) in hepatocellular carcinoma (HCC) progression. We showed that CAFs secrete high levels of IL-6, which promoted stem cell-like properties in HCC cells by activating Notch signaling through STAT3 Tyr705 phosphorylation. These effects were abolished by Notch1 shRNA knockdown in HCC cells or treatment with an IL-6 neutralizing antibody or the p-STAT3 (Tyr705) inhibitor cryptotanshinone. Xenografted liver tumors were larger in nude mice injected with HCC cells and CAFs than in those receiving HCC cells alone. Moreover, immunohistochemical analysis of liver tissue specimens from 88 HCC patients revealed that high nuclear Notch intracellular domain (nNICD) levels in HCC cells correlated with poor prognosis in patients. These findings suggest that IL-6 secreted by CAFs promotes stem cell-like properties in HCC cells by enhancing STAT3/Notch signaling.
基金:
National Natural Science Foundation of China [81172063, 81372352]
第一作者单位:[1]Huazhong Univ Sci & Technol,Tongji Med Coll,Tongji Hosp,Dept Gastroenterol & Hepatol,Wuhan 430030,Hubei,Peoples R China
通讯作者:
推荐引用方式(GB/T 7714):
Xiong Si,Wang Ronghua,Chen Qian,et al.Cancer-associated fibroblasts promote stem cell-like properties of hepatocellular carcinoma cells through IL-6/STAT3/Notch signaling[J].AMERICAN JOURNAL OF CANCER RESEARCH.2018,8(2):302-+.
APA:
Xiong, Si,Wang, Ronghua,Chen, Qian,Luo, Jing,Wang, Jinlin...&Cheng, Bin.(2018).Cancer-associated fibroblasts promote stem cell-like properties of hepatocellular carcinoma cells through IL-6/STAT3/Notch signaling.AMERICAN JOURNAL OF CANCER RESEARCH,8,(2)
MLA:
Xiong, Si,et al."Cancer-associated fibroblasts promote stem cell-like properties of hepatocellular carcinoma cells through IL-6/STAT3/Notch signaling".AMERICAN JOURNAL OF CANCER RESEARCH 8..2(2018):302-+