Ginkgolic Acid, a SUMO-1 Inhibitor, Inhibits the Progression of Oral Squamous Cell Carcinoma by Alleviating SUMOylation of SMAD4
| Autor: | Dong-Yang Xu, Wenfeng Chu, Duo Li, Ke Liu, Dan Zhao, Xiaofeng Wang, De-Zhi Li, Xinhuan Wang, Zhiyong Lv |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research proliferation Cell SUMO protein migration lcsh:RC254-282 Article 03 medical and health sciences 0302 clinical medicine Ubiquitin medicine Pharmacology (medical) ginkgolic acid small ubiquitin-like modifiers biology Cell growth Chemistry Cell migration lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens oral squamous cell carcinoma stomatognathic diseases 030104 developmental biology medicine.anatomical_structure Oncology Apoptosis Cell culture Tumor progression 030220 oncology & carcinogenesis biology.protein Cancer research Molecular Medicine |
| Zdroj: | Molecular Therapy Oncolytics Molecular Therapy: Oncolytics, Vol 16, Iss, Pp 86-99 (2020) |
| ISSN: | 2372-7705 |
| Popis: | Small ubiquitin-related modifiers (SUMO) represent a class of ubiquitin-like proteins that are conjugated, like ubiquitin, by a set of enzymes to form cellular regulatory proteins, and play key roles in the control of cell proliferation, differentiation, and apoptosis. We found that ginkgolic acid (GA) can significantly reduce cell vitality in a dose- and time-dependent manner and can also accelerate cyto-apoptosis in both Tca8113 and Cal-27 cells. Migration and wound-healing assays were executed to determine the anti-migration effect of GA in oral squamous cell carcinoma (OSCC) cell lines. GA represses transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) markers in OSCC cell lines. This investigation is the first evidence that GA suppresses TGF-β1-induced SUMOylation of SMAD4. We show that GA affects the phosphorylation of SMAD2/3 protein and the release of SMAD4. In the xenograft mouse model, the OSCC progression was reduced by GA, effectively suppressing the growth of tumors. In addition, siSMAD4 improved cell migration and viability, which was inhibited by GA in Tca8113 cells. GA suppresses tumorigenicity and tumor progression of OSCC through inhibition of TGF-β1-induced enhancement of SUMOylation of SMAD4. Thus, GA could be a promising therapeutic for OSCC. Graphical Abstract |
| Databáze: | OpenAIRE |
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