Metformin reduces TRIB3 expression and restores autophagy flux: an alternative antitumor action
| العنوان: | Metformin reduces TRIB3 expression and restores autophagy flux: an alternative antitumor action |
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| المؤلفون: | Zhuo-Wei Hu, Fang Hua, Ting-ting Zhang, Ke Li |
| المصدر: | Autophagy. 14:1278-1279 |
| بيانات النشر: | Informa UK Limited, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Antineoplastic Agents, Biology, Models, Biological, 03 medical and health sciences, 0302 clinical medicine, Autophagy, medicine, Animals, Smad3 Protein, Epigenetics, KAT5, Melanoma, Molecular Biology, Lysine Acetyltransferase 5, Cell Biology, Metformin, Mice, Inbred C57BL, Repressor Proteins, 030104 developmental biology, Tumor progression, 030220 oncology & carcinogenesis, Disease Progression, Commentary, Cancer research, Phosphorylation, Flux (metabolism), medicine.drug |
| الوصف: | Deregulation of metabolism during melanoma progression is tightly associated with the genetic and epigenetic alterations of metabolic regulators. Metformin, a macroautophagy/autophagy inducer, has beneficial effects of preventing and treating multiple cancers with an unclear mechanism. Enhanced pseudokinase TRIB3 was reported to link metabolic stressors to melanoma promotion by inhibiting autophagy and ubiquitin-proteasome degradation systems. Here, we discuss our recent findings regarding how metformin reduces TRIB3 expression to restore autophagic flux and suppress melanoma progression in non-diabetic and diabetic mice. We found that overexpression of TRIB3 reverses the metformin-activated autophagic flux, clearance of accumulated tumor-promoting factors and inhibition of tumor progression. Mechanistically, TRIB3 interacts with KAT5 (lysine acetyltransferase 5) and promotes the physical association of KAT5 and SMAD3, which enhances SMAD3 K333 acetylation in a phosphorylation-dependent manner, sustains SMAD3 transcriptional activity and induces TRIB3 expression. Metformin inhibits SMAD3 phosphorylation and impedes the KAT5-SMAD3 interaction, which attenuates the KAT5-mediated K333 acetylation of SMAD3 to suppress SMAD3 transcriptional activity and TRIB3 expression. Our finding defines a molecular mechanism by which metformin targets TRIB3 expression to induce autophagy and protect against melanoma progression. |
| تدمد: | 1554-8635 1554-8627 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b76d5a78872247f23f8b2ebae0a73a2fTest https://doi.org/10.1080/15548627.2018.1460022Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b76d5a78872247f23f8b2ebae0a73a2f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15548635 15548627 |
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