Alpha-fetoprotein inhibits autophagy to promote malignant behaviour in hepatocellular carcinoma cells by activating PI3K/AKT/mTOR signalling.
Alpha-fetoprotein inhibits autophagy to promote malignant behaviour in hepatocellular carcinoma cells by activating PI3K/AKT/mTOR signalling.
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甲胎蛋白通过激活 PI3K/AKT/mTOR 信号传导抑制自噬，促进肝细胞癌细胞的恶性行为。
DOI：
10.1038/s41419-018-1036-5
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发表时间：
2018-10-09
影响因子：
9
通讯作者：
Li M
中科院分区：
文献类型：
--
作者：
Wang S;Zhu M;Wang Q;Hou Y;Li L;Weng H;Zhao Y;Chen D;Ding H;Guo J;Li M
甲胎蛋白（AFP）是肝细胞癌（HCC）细胞增殖的关键调节因子。然而，AFP是否在癌细胞自噬中起作用仍不清楚。本研究探讨AFP对肝癌细胞自噬的影响。在两个肝癌细胞系PLC/PRF/5和HLE中研究了AFP的作用。采用Western blotting、免疫共沉淀（CoIP）、免疫荧光、动物模型、MTT法、流式细胞术（FCM）、细胞计数试剂盒（CCK）-8、划痕法和transwell法检测细胞自噬、凋亡、增殖、迁移和侵袭。在PLC/PRF/5细胞中，AFP与PTEN相互作用并激活PI 3 K/Akt/mTOR信号通路。在HLE细胞中，过表达的AFP类似地与PTEN相互作用，导致PI 3 K/Akt/mTOR活化和细胞自噬减少。当AFP沉默PLC/PRF/5细胞时，细胞增殖、肿瘤生长、迁移和侵袭受到抑制，S期细胞和凋亡细胞数量增加。与此相反，AFP在HLE细胞中的过表达促进细胞增殖、迁移和侵袭，并减少凋亡。雷帕霉素可抑制AFP依赖的自噬、增殖、迁移和凋亡。总之，AFP在抑制肝癌细胞的自噬和凋亡中起关键作用，并促进增殖、迁移和侵袭。AFP在肝癌细胞自噬抑制中的作用可能涉及PI 3 K/Akt/mTOR信号转导的激活。
Alpha-fetoprotein (AFP) has been recognized as a key regulator of cell proliferation in hepatocellular carcinoma (HCC). However, whether AFP functions in cancer cell autophagy remains unknown. This study investigated the effects of AFP on autophagy in HCC cells. The role of AFP was studied in two HCC cell lines, PLC/PRF/5 and HLE. Cell autophagy, apoptosis, proliferation, migration and invasion were analysed with Western blotting, co-immunoprecipitation (CoIP), immunofluorescence, animal models, MTT assays, flow cytometry (FCM), Cell Counting Kit (CCK)-8, and scratch and transwell assays. In PLC/PRF/5 cells, AFP interacted with PTEN and activated PI3K/Akt/mTOR signalling. In HLE cells, overexpressed AFP similarly interacted with PTEN, leading to PI3K/Akt/mTOR activation and reduced cell autophagy. When AFP was silenced in PLC/PRF/5 cells, cell proliferation, tumour growth, migration and invasion were inhibited, and the numbers of S-phase and apoptotic cells were increased. In contrast, AFP overexpression in HLE cells enhanced cell proliferation, migration and invasion and reduced apoptosis. AFP-dependent autophagy, proliferation, migration and apoptosis were inhibited by rapamycin. In summary, AFP plays critical roles in the inhibition of autophagy and apoptosis in HCC cells and promotes proliferation, migration and invasion. The role of AFP in autophagy inhibition in HCC cells may involve the activation of PI3K/Akt/mTOR signalling.
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影响因子：
--
作者：
Jiang, Bing-Hua;Liu, Ling-Zhi
通讯作者：
Liu, Ling-Zhi
HepG2细胞中EGCG介导的AFP自噬调节的新分子机制
影响因子：
9
作者：
Zhao L;Liu S;Xu J;Li W;Duan G;Wang H;Yang H;Yang Z;Zhou R
通讯作者：
Zhou R
影响因子：
9.3
作者：
Hou X;Hu Z;Xu H;Xu J;Zhang S;Zhong Y;He X;Wang N
通讯作者：
Wang N
影响因子：
13.3
作者：
Saiki, Shinji;Sasazawa, Yukiko;Hattori, Nobutaka
通讯作者：
Hattori, Nobutaka
影响因子：
4
作者：
Duvoux, Christophe;Toso, Christian
通讯作者：
Toso, Christian