MilliporeSigma
  • 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.

Cell death & disease (2018-10-12)
Shanshan Wang, Mingyue Zhu, Qiaoyun Wang, Yuli Hou, Lei Li, Honglei Weng, Yan Zhao, Dexi Chen, Huiguo Ding, Junli Guo, Mengsen Li
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
MISSION® esiRNA, targeting human AFP
Millipore
ANTI-FLAG® antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution