Research Paper Volume 12, Issue 12 pp 11812—11834

FAM83H and SCRIB stabilize β-catenin and stimulate progression of gastric carcinoma

Usama Khamis Hussein1,2,3, *, , Sang Hoon Ha4, *, , Asmaa Gamal Ahmed1,5, *, , Kyoung Min Kim1,2, , See-Hyoung Park6, , Chan Young Kim2,7, , Keun Sang Kwon8, , Zhongkai Zhang1, , Sang-A Lee1, , Ho Sung Park1,2, , Byung-Hyun Park9, , Ho Lee10, , Myoung Ja Chung1,2, , Woo Sung Moon1,2, , Myoung Jae Kang1,2, , Kyu Yun Jang1,2, ,

  • 1 Department of Pathology, Jeonbuk National University Medical School, Jeonju, Republic of Korea
  • 2 Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea
  • 3 Faculty of Science, Beni-Suef University, Beni-Suef, Egypt
  • 4 Division of Biotechnology, Jeonbuk National University, Iksan, Republic of Korea
  • 5 Faculty of Postgraduate Studies and Advanced Sciences, Beni-Suef University, Beni-Suef, Egypt
  • 6 Department of Bio and Chemical Engineering, Hongik University, Sejong, Republic of Korea
  • 7 Department of Surgery, Jeonbuk National University Medical School, Jeonju, Republic of Korea
  • 8 Department of Preventive Medicine, Jeonbuk National University Medical School, Jeonju, Republic of Korea
  • 9 Department of Biochemistry, Jeonbuk National University Medical School, Jeonju, Republic of Korea
  • 10 Department of Forensic Medicine, Jeonbuk National University Medical School, Jeonju, Republic of Korea
* Equal contribution

Received: October 4, 2019       Accepted: May 14, 2020       Published: June 20, 2020      

https://doi.org/10.18632/aging.103351
How to Cite

Copyright © 2020 Hussein 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.

Abstract

FAM83H primarily is known for its function in tooth development. Recently, a role for FAM83H in tumorigenesis, conjunction with MYC and β-catenin, has been suggested. Analysis of public data indicates that FAM83H expression is closely associated with SCRIB expression in human gastric cancers. Therefore, this study investigated the roles of FAM83H and SCRIB in 200 human gastric cancers and gastric cancer cells. In human gastric carcinomas, both the individual and combined expression patterns of the nuclear FAM83H and SCRIB were independent indicators of shorter survival of gastric carcinoma patients. In MKN-45 and NCI-N87 gastric cancer cells, the expression of FAM83H and SCRIB were associated with proliferation and invasiveness of cells. FAM83H-mediated in vivo tumor growth was attenuated with knock-down of SCRIB. Moreover, immunoprecipitation indicates that FAM83H, SCRIB, and β-catenin, form a complex, and knock-down of either FAM83H or SCRIB accelerated proteasomal degradation of β-catenin. In conclusion, this study has found that the individual and combined expression patterns of nuclear FAM83H and SCRIB are prognostic indicators of gastric carcinomas and further suggests that FAM83H and SCRIB are involved in the progression of gastric carcinomas by stabilizing β-catenin.

Abbreviations

95% CI: 95% confidence interval; β-catenin-N: nuclear expression of β-catenin; EMT: epithelial-to-mesenchymal transition; FAM83H-C: cytoplasmic expression of FAM83H; FAM83H-N: nuclear expression of FAM83H; HR: hazard ratio; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-iphenyltetrazolium bromide; OS: overall survival; RFS: relapse-free survival; SCRIB-C: cytoplasmic expression of SCRIB; SCRIB-N: nuclear expression of SCRIB.