Research Paper Volume 13, Issue 17 pp 21202—21215

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

Minfen Zhang1,3, *, , Hui Chen1, *, , Ping Qin1, , Tonghui Cai1, , Lingjun Li1, , Ruichao Chen1, , Shaoyan Liu1, , Hui Chen3, , Wanrun Lin4, , Hao Chen4, , Amanda L. Strickland5, , Hanzhen Xiong1, &, , Qingping Jiang1,2, ,

  • 1 Department of Pathology, Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
  • 2 Key Laboratory of Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
  • 3 Department of Pathology, First Affiliated Hospital, Changsha 410005, China
  • 4 Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
  • 5 Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
* Equal contribution

Received: May 11, 2020       Accepted: July 30, 2021       Published: September 14, 2021
How to Cite

Copyright: © 2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


EEC: Endometrioid endometrial carcinoma; EC: Endometrial carcinoma; NMD: Nonsense-mediated mRNA degradation; mTOR: Mammalian target of rapamycin; UPF1: Up-frameshift 1, a key protein factor in the NMD pathway; mTOR1: mTOR complex 1; mTOR2: mTOR complex 2; p70s6k: protein 40S ribosomal protein S6 kinase; PTCs: premature stop codons; HCC: Hepatic Cellular Cancer; ASC: adenosquamous carcinoma; Atg: autophagy-related proteins; Beclin1: programmed cell death-1; LC3: a marker of autophagic membrane; P62: a commonly used marker for autophagy degradation; MALAT1: metastasis associated lung adenocarcinoma transcript 1; IHC: Immunohistochemistry staining; qRT-PCR: quantitative real-time PCR; FACS: Fluorescence-activated cell sorting.