MOF upregulates the estrogen receptor α signaling pathway by its acetylase activity in hepatocellular carcinoma
| العنوان: | MOF upregulates the estrogen receptor α signaling pathway by its acetylase activity in hepatocellular carcinoma |
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| المؤلفون: | Ning Sun, Kai Zeng, Shan Wei, Chunyu Wang, Huijuan Song, Baosheng Zhou, Manlin Wang, Wei Liu, Yi Wu, Fan Yang, Lin Lin, Ruina Luan, Yue Zhao, Renlong Zou, Shengli Wang |
| المصدر: | Cancer Science |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Cancer Research, Estrogen receptor, Kaplan-Meier Estimate, Histones, Mice, Transactivation, 0302 clinical medicine, Cell, Molecular, and Stem Cell Biology, Cell Movement, Databases, Genetic, Histone Acetyltransferases, biology, Chemistry, Liver Neoplasms, hepatocellular carcinoma, General Medicine, Middle Aged, Up-Regulation, Oncology, 030220 oncology & carcinogenesis, Heterografts, Original Article, Female, tumor suppression, Signal transduction, Signal Transduction, Transcriptional Activation, Carcinoma, Hepatocellular, Down-Regulation, Antibodies, Histone H4, 03 medical and health sciences, Downregulation and upregulation, Animals, Humans, Neoplasm Invasiveness, acetylation, MOF, Cell Proliferation, Cell growth, Lysine, fungi, Estrogen Receptor alpha, Ubiquitination, estrogen receptor α, Original Articles, Histone acetyltransferase, digestive system diseases, 030104 developmental biology, Acetylation, biology.protein, Cancer research, Acetylesterase |
| الوصف: | The histone acetyltransferase MOF (KAT8) is mainly involved in the acetylation of histone H4 at lysine 16 (H4K16) and some non‐histone proteins. The MOF expression level is significantly reduced in many cancers, however the biological function of MOF and its underlying mechanism are still elusive in hepatocellular carcinoma (HCC). Estrogen receptor α (ERα) has been considered as a tumor suppressor in HCC. Here, we demonstrated that MOF expression is significantly reduced in HCC samples, and is positively correlated with that of ERα. MOF interacts with ERα, and participates in acetylation of ERα at K266, K268, K299, thereby inhibiting ERα ubiquitination to maintain the stability of ERα. In addition, MOF participates in the upregulation of ERα‐mediated transactivation. Depletion of MOF significantly promotes cell growth, migration, and invasion in HCC cell lines. Taken together, our results provide new insights to understand the mechanism underlying the modulation function of MOF on ERα action in HCC, suggesting that MOF might be a potential therapeutic target for HCC. In summary, we have demonstrated that MOF as a crucial histone acetylase participates in the acetylation of ERα, thereby inhibiting the ubiquitination of ERα to stabilize ERα protein in HCC. MOF upregulates ERα‐induced transactivation. MOF depletion promotes the cell proliferation, migration, and invasion in HCC cells. |
| تدمد: | 1349-7006 1347-9032 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::78486e542162fe357f9490bc20063aa0Test https://doi.org/10.1111/cas.14836Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....78486e542162fe357f9490bc20063aa0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13497006 13479032 |
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