1. Academic Validation
  2. Involvement of TOB1 on autophagy in gastric cancer AGS cells via decreasing the activation of AKT/mTOR signaling pathway

Involvement of TOB1 on autophagy in gastric cancer AGS cells via decreasing the activation of AKT/mTOR signaling pathway

  • PeerJ. 2022 Feb 4;10:e12904. doi: 10.7717/peerj.12904.
Dong Wang  # 1 Yunlong Li  # 2 Shuning Sui 1 Mengdi Cai 3 Kexian Dong 3 Ping Wang 3 Xiao Liang 3 Songbin Fu 3 Jingcui Yu 1
Affiliations

Affiliations

  • 1 Scientific Research Centre, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • 2 Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • 3 Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China, Ministry of Education, Harbin Medical University, Harbin, China.
  • # Contributed equally.
Abstract

Background: We previously identified the tumor suppressor gene TOB1 as related to gastric Cancer. The purpose of this study was to explore whether TOB1 induces Autophagy through the Akt/mTOR signaling pathway in gastric Cancer.

Methods: Western blotting was used to detect the protein levels of TOB1, LC3, Akt, mTOR, phosphorylated (p) Akt, and p-mTOR. A double fluorescent GFP-RFP-LC3 fusion protein was used to trace Autophagy by laser confocal microscopy. Autophagosomes were observed by transmission electron microscopy.

Results: The conversion of LC3-I to LC3-II and the LC3-II/LC3-I ratio were significantly increased in AGS cells overexpressing TOB1 compared with control cells. Fluorescence imaging showed LC3 puncta at 48 h, and these puncta increased significantly at 72 h after TOB1 transfection compared with control tumor cells. The presence of autophagosomes in AGS cells was observed at 72 h after TOB1 transfection by transmission electron microscopy, and no autophagosomes were found in the control cells. Moreover, the levels of p-AKT and p -mTOR were lower in AGS cells than in control Cancer cells.

Conclusion: Our results provide novel insight that TOB1 might suppress gastric Cancer by inducing Autophagy, possibly through decreasing phosphorylation and the subsequent activation of the Akt/mTOR signaling pathway.

Keywords

AKT/mTOR signaling pathway; Autophagy; Gastric cancer; TOB1 gene.

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