Department of Pathology, Jeonbuk National University Medical School, Jeonju, Republic of Korea.
Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea.
Aging (Albany NY). 2020 Jun 20;12(12):11812-11834. doi: 10.18632/aging.103351.
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 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.
FAM83H 主要因其在牙齿发育中的功能而为人所知。最近，有人提出 FAM83H 与 MYC 和 β-连环蛋白一起在肿瘤发生中起作用。对公共数据的分析表明，FAM83H 的表达与人胃腺癌中 SCRIB 的表达密切相关。因此，本研究在 200 例人类胃癌和胃癌细胞中研究了 FAM83H 和 SCRIB 的作用。在人类胃腺癌中，核 FAM83H 和 SCRIB 的单独和联合表达模式均是胃癌患者生存时间较短的独立指标。在 MKN-45 和 NCI-N87 胃癌细胞中，FAM83H 和 SCRIB 的表达与细胞的增殖和侵袭性有关。敲低 SCRIB 可减弱 FAM83H 介导的肿瘤生长。此外，免疫沉淀表明 FAM83H、SCRIB 和 β-连环蛋白形成复合物，敲低 FAM83H 或 SCRIB 均可加速 β-连环蛋白的蛋白酶体降解。总之，本研究发现核 FAM83H 和 SCRIB 的单独和联合表达模式是胃癌的预后指标，并进一步表明 FAM83H 和 SCRIB 通过稳定 β-连环蛋白参与胃癌的进展。
