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
✉ Corresponding authors: Qingguang Liu MD., Ph.D., Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, 710061 Xi`an, China, E-mail: xhg1982_xjtucom OR Xin Zheng MD., Ph.D., Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, 710061 Xi`an, China, E-mail: ye2312xjtu.edu.cnMore
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. https://www.jcancer.org/v11p0570.htm
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.
Gai, X., Zhou, P., Xu, M., Liu, Z., Zheng, X., Liu, Q. (2020). 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. Journal of Cancer, 11(3), 570-582. https://doi.org/10.7150/jca.35631.
ACS
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.
NLM
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. https://www.jcancer.org/v11p0570.htm
CSE
Gai X, Zhou P, Xu M, Liu Z, Zheng X, Liu Q. 2020. 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. 11(3):570-582.
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