2. Academic Validation
  3. S119N Mutation of the E3 Ubiquitin Ligase SPOP Suppresses SLC7A1 Degradation to Regulate Hepatoblastoma Progression

S119N Mutation of the E3 Ubiquitin Ligase SPOP Suppresses SLC7A1 Degradation to Regulate Hepatoblastoma Progression

  • Mol Ther Oncolytics. 2020 Oct 4:19:149-162. doi: 10.1016/j.omto.2020.09.008.
Weijing He 1 2,  Jingjing Zhang 3,  Baihui Liu 1 2,  Xiangqi Liu 1 2,  Gongbao Liu 1 2,  Lulu Xie 1 2,  Jiajun He 1 2,  Meng Wei 1 2,  Kai Li 1 2,  Jing Ma 4,  Rui Dong 1 2,  Duan Ma 5 6,  Kuiran Dong 1 2,  Mujie Ye 1 2
Affiliations

Affiliations

  • 1 Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai 201102, China.
  • 2 Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 201102, China.
  • 3 Department of Medical Imaging, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210001, China.
  • 4 ENT Institute, Department of Facial Plastic and Reconstructive Surgery, Eye and ENT Hospital, Fudan University, Shanghai 200031, China.
  • 5 Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institute of Biomedical Sciences, Collaborative Innovation Center of Genetics and Development, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
  • 6 Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai 201102, China.
PMID: 33209975 DOI: 10.1016/j.omto.2020.09.008
Abstract

A previous study on hepatoblastoma revealed novel mutations and Cancer genes in the Wnt pathway and ubiquitin Ligase complex, including the tumor suppressor speckle-type BTB/POZ (SPOP). Moreover, the SPOP gene affected cell growth, and its S119N mutation was identified as a loss-of-function mutation in hepatoblastoma. This study aimed to explore more functions and the potential mechanism of SPOP and its S119N mutation. The in vitro effects of SPOP on cell proliferation, invasion, Apoptosis, and in vivo tumor growth were investigated by western blot analysis, Cell Counting Kit-8, colony formation assay, flow cytometry, and xenograft animal experiments. The substrate of SPOP was discovered by a protein quantification assay and quantitative ubiquitination modification assay. The present study further proved that SPOP functioned as an anti-oncogene through the phosphatidylinositol 3-kinase/Akt signaling pathway to affect various malignant biological behaviors of hepatoblastoma both in vitro and in vivo. Furthermore, experimental results also suggested that solute carrier family 7 member 1 (SLC7A1) might be a substrate of SPOP and influence cell phenotype by regulating arginine metabolism. In conclusion, these findings demonstrated the function of SPOP and revealed a potential substrate related to hepatoblastoma tumorigenesis, which might thus provide a novel therapeutic target for hepatoblastoma.

Keywords

amino acid metabolism; epithelial-mesenchymal transition; hepatoblastoma; mutation; ubiquitin degradation.

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