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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
  • 1Department of Pathology, Jeonbuk National University Medical School, Jeonju, Republic of Korea
  • 2Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea
  • 3Faculty of Science, Beni-Suef University, Beni-Suef, Egypt
  • 4Division of Biotechnology, Jeonbuk National University, Iksan, Republic of Korea
  • 5Faculty of Postgraduate Studies and Advanced Sciences, Beni-Suef University, Beni-Suef, Egypt
  • 6Department of Bio and Chemical Engineering, Hongik University, Sejong, Republic of Korea
  • 7Department of Surgery, Jeonbuk National University Medical School, Jeonju, Republic of Korea
  • 8Department of Preventive Medicine, Jeonbuk National University Medical School, Jeonju, Republic of Korea
  • 9Department of Biochemistry, Jeonbuk National University Medical School, Jeonju, Republic of Korea
  • 10Department of Forensic Medicine, Jeonbuk National University Medical School, Jeonju, Republic of Korea
* Equal contribution
Received: October 4, 2019Accepted: May 14, 2020Published: June 20, 2020
https://doi.org/10.18632/aging.103351

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.