Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, 321, Zhongshan Road, 210008, Nanjing, Jiangsu Province, China.
Cell Death Dis. 2018 Feb 14;9(2):225. doi: 10.1038/s41419-018-0329-z.
The receptor for advanced glycation end products (Rage) is involved in the development of various tumors and acts as an oncogenic protein. Rage is overexpressed in tumors including hepatocellular carcinoma (HCC). However, the molecular mechanism of Rage in HCC progression and sorafenib resistance remains unclear. In this study, enhanced Rage expression is highly associated proliferation and contributes to sorafenib resistance. Rage deficiency contributed to autophagy induction through activating AMPK/mTOR signaling pathway, which is important for sorafenib response. Moreover, the interactions between Rage and Rage ligands such as high mobility group box 1 (HMGB1) and s100a4 positively increased Rage expression. Our data indicate that Rage may be a potential target for therapeutic intervention in HCC and biomarker for sorafenib resistance.
晚期糖基化终产物受体（Rage）参与多种肿瘤的发生发展，并作为一种癌蛋白发挥作用。Rage 在包括肝细胞癌（HCC）在内的肿瘤中过表达。然而，Rage 在 HCC 进展和索拉非尼耐药中的分子机制尚不清楚。在这项研究中，增强的 Rage 表达与增殖高度相关，并导致索拉非尼耐药。Rage 缺乏通过激活 AMPK/mTOR 信号通路促进自噬诱导，这对于索拉非尼反应很重要。此外，Rage 与其配体如高迁移率族蛋白 B1（HMGB1）和 S100A4 之间的相互作用可正向增加 Rage 表达。我们的数据表明，Rage 可能是 HCC 治疗干预的潜在靶点和索拉非尼耐药的生物标志物。
