J Cancer 2020; 11(3):570-582. doi:10.7150/jca.35631

Research Paper

Hyperactivation of IL-6/STAT3 pathway leaded to the poor prognosis of post-TACE HCCs by HIF-1α/SNAI1 axis-induced epithelial to mesenchymal transition

Xiaohong Gai1, Peng Zhou2, Meng Xu1, Zhikui Liu1, Xin Zheng1✉, Qingguang Liu1✉

1. Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
2. Department of General Surgery, Xian NO.3 Hospital, Xi'an, Shaanxi 710001, China

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Gai X, Zhou P, Xu M, Liu Z, Zheng X, Liu Q. Hyperactivation of IL-6/STAT3 pathway leaded to the poor prognosis of post-TACE HCCs by HIF-1α/SNAI1 axis-induced epithelial to mesenchymal transition. J Cancer 2020; 11(3):570-582. doi:10.7150/jca.35631. Available from http://www.jcancer.org/v11p0570.htm

File import instruction

Abstract

Transarterial chemoembolization (TACE) has been considered the standard treatment for intermediate-stage hepatocellular carcinoma according to BCLC algorithm. However, it has been unclear about the TACE-related predictive bio-markers and underlying molecular mechanisms. This investigation revealed that HCCs with higher HIF-1α suffered from unfavorable OS after TACE. mRNA expression microarray revealed that HIF-1α was potential target of p-STAT3 which was verified by ChIP and immunoblotting assay. Activation of IL-6/STAT3/HIF-1α signaling was found to promote EMT and chemoresistance to Doxorubicin in vitro and in vivo by regulating SNAI1. Hypoxia did not enhance HIF-1α expression and influence cell growth and chemoresistence to Doxorubicin in HCC cells when STAT3 expression was abolished. Taken together, HIF-1α overexpression in HCC tissues predicted the unfavorable outcome of HCCs after TACE and IL-6/STAT3 pathway resulted in EMT induced-metastases and chemoresistance of HCC after TACE through HIF-1α/SNAI1 axis.

Keywords: IL-6/STAT3 signaling, HCC, TACE, HIF-1α, SNAI1