Aberrant accumulation of NIK promotes tumorigenicity by dysregulating post-translational modifications in breast cancer
Aberrant accumulation of NIK promotes tumorigenicity by dysregulating post-translational modifications in breast cancer
Abstract Post-translational modifications and mRNA translation are frequently altered in human cancers. However, investigations to understand their roles in the cancer progression mechanism remain insufficient. In this research, we explored protein levels altered by translational or post-translational regulation by analyzing transcriptome and western blotting data of the highly malignant breast cancer cell lines. From these analyses, NIK was found to be upregulated at the protein level to predominantly activate the non-canonical NF-κB pathway in a breast cancer cell line. Furthermore, the increase in NIK protein production was attributed to the dysregulation of ubiquitin-proteasome system caused by a decrease in the translation of cIAP1. NIK upregulation contributed to tumorigenicity by regulating the expression of inflammatory response-related genes. Collectively, our study suggests that NIK is post-translationally modified and has the potential to be a therapeutic target and diagnostic marker for breast cancer.
Higashiyama Shigeki、Inoue Jun-ichiro、Yamamoto Yusuke、Maekawa Masashi、Semba Kentaro、Hayashi Yusuke、Nakayama Jun、Watanabe Shinya、Yamamoto Mizuki
Division of Cell Growth and Tumor Regulation, Proteo-Science Center, Ehime University||Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine||Department of Molecular and Cellular Biology, Osaka International Cancer InstituteResearch Platform Office, The Institute of Medical Science, The University of TokyoLaboratory of Integrative Oncology, National Cancer Center Research InstituteDivision of Cell Growth and Tumor Regulation, Proteo-Science Center, Ehime University||Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of MedicineDepartment of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University||Translational Research Center, Fukushima Medical UniversityDepartment of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University||Laboratory of Integrative Oncology, National Cancer Center Research InstituteDepartment of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University||Laboratory of Integrative Oncology, National Cancer Center Research InstituteTranslational Research Center, Fukushima Medical UniversityResearch Center for Asian Infectious Diseases, The Institute of Medical Science, The University of Tokyo
肿瘤学基础医学生物化学
NIKNon-canonical NF-κBPost-translational regulationin vivo selectionOrthotopic xenograftBreast cancer
Higashiyama Shigeki,Inoue Jun-ichiro,Yamamoto Yusuke,Maekawa Masashi,Semba Kentaro,Hayashi Yusuke,Nakayama Jun,Watanabe Shinya,Yamamoto Mizuki.Aberrant accumulation of NIK promotes tumorigenicity by dysregulating post-translational modifications in breast cancer[EB/OL].(2025-03-28)[2025-05-28].https://www.biorxiv.org/content/10.1101/2021.08.27.457878.点此复制
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