UPF1 impacts on mTOR signaling pathway and autophagy in endometrioid endometrial carcinoma

Minfen Zhang, Hui Chen, Ping Qin, Tonghui Cai, Lingjun Li, Ruichao Chen, Shaoyan Liu, Hui Chen, Wanrun Lin, Hao Chen, Amanda L. Strickland, Hanzhen Xiong, Qingping Jiang

Research output: Contribution to journalArticlepeer-review

Abstract

Most EEC cases are associated with activities of the mTOR pathway, which regulates protein synthesis, cell growth and autophagy. While Up-Frameshift 1(UPF1) is a key protein factor in the nonsense-mediated mRNA degradation pathway (NMD), its role in carcinogenesis of EEC remains unclear. In this study, we first evaluated the expression level of UPF1 in EEC tissues and cell lines. Then, we investigated the effect of UPF1 on cellular function and mTOR signaling pathway; these effects were further validated in vivo. Finally, its effect on autophagy was evaluated by western blot and GFP-mRFP-LC3 staining. UPF1 expression in the EEC tissue samples was significantly higher than that of matched normal tissue samples. Overexpression of UPF1 promoted migration and invasion of EEC cells. Conversely, depletion of UPF1 suppressed migration and invasion of EEC cells. In addition, overexpression of UPF1 increased the in vivo growth of our EEC xenograft tumors. Finally, UPF1 increased the activity of the mTOR/P70S6K/4EBP1 signaling pathway and inhibited autophagy in EEC cells. These findings suggest that UPF1 functions as an oncogene to promote EEC carcinogenesis. Our findings propose UPF1 as a new potential therapeutic target for EEC

Original languageEnglish (US)
Pages (from-to)21202-21215
Number of pages14
JournalAging
Volume13
Issue number17
DOIs
StatePublished - Sep 15 2021

Keywords

  • UPF1
  • autophagy
  • endometrioid endometrial carcinoma
  • mTOR

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Fingerprint

Dive into the research topics of 'UPF1 impacts on mTOR signaling pathway and autophagy in endometrioid endometrial carcinoma'. Together they form a unique fingerprint.

Cite this