标题：Upregulation of BNIP3 mediated by ERK/HIF-1 alpha pathway induces autophagy and contributes to anoikis resistance of hepatocellular carcinoma cells
作者：Sun, Lei;Li, Tao;Wei, Qing;Zhang, Ying;Jia, Xiaoqing;Wan, Zhengkun;Han, Lihui
作者机构：[Sun, L] Department of Immunology, Shandong University School of Medicine, Jinan 250012, China;[ Li, T] Department of Immunology, Shandong University 更多
通讯作者地址：[Han, LH]Shandong Univ, Sch Med, Dept Immunol, Jinan 250012, Peoples R China.
关键词：anoikis resistance;autophagy;BNIP3;hepatocellular carcinoma;mTOR/S6K1
摘要：Aim: Acquisition of anoikis resistance is the hallmark of cancer and has been shown to be involved in metastasis of melignant cells. Our previous work showed that anoikis resistance is associated with the metastasis of hepatocellular carcinoma (HCC) cells. The aim of this study is to elucidate the mechanisms of this course. Materials & methods: Expression of BNIP3 and HIF-1 alpha at the mRNA and protein level in HCC cells were detected by realtime PCR and western blot, respectively. Autophagy activation and signaling transduction pathway were detected by western blot. Cell viabilities were detected by CCK8 assay and trypan blue exclusion assay. Results: Upregulation of BNIP3 promoted the activation of autophagy, one type of cell survival strategy in response to external stress, by suppressing mTOR/S6K1 signaling system. The upregulation of BNIP3 was mediated by ERK/HIF-1 alpha pathway, which further contributed to anoikis resistance of HCC cells through the mTORC1 signaling pathway. Conclusion: Upregulation of BNIP3 contributs to anoikis resistance of HCC cells, and BNIP3 may serve as a novel therapeutic target for manipulation of cancer metastasis.