Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 138, Issue 2, Pages 89-95Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1016/j.jphs.2018.07.013
Keywords
Yes-Associated Protein (YAP); Interleukin-6 (IL-6); Tumor-associated macrophages (TAMs); Tumor microenvironment; Hepatocellular carcinoma
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Funding
- Zhejiang Medical Technology Education [2016KYA053]
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Tumor-associated macrophages (TAMs) has been regarded as the most prominent component in tumor microenvironment. The correlation between TAM density and poor prognosis in Hepatocellular carcinoma (HCC) patients suggests a supportive role for TAMs in tumor progression. Here we employed a co-culture system to interrogate the molecular link between Yes-Associated Protein (YAP) and TAMs chemotaxis in HCC cells. We found that YAP activation was critical for the recruitment of TAMs towards HCC cells. Furthermore, cytokine array and quantitative RT-PCR analyses showed that IL-6 secreted by YAP-activated HCC cells might induce the TAMs recruitment. Interrupting YAP function by statins, the inhibitors of hydroxymethylglutaryl-CoA reductase, could robustly suppress the chemotaxis of TAMs. Together with our findings that the expression levels ofIL-6inhumanHCC tumors were highly correlated with the prognosis of HCC patients, the current study highlight the possibility of improving HCC treatment by targeting YAP-IL-6 mediated TAMs recruitment. (c) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.
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