Tunicamycin inhibits cell proliferation and migration in hepatocellular carcinoma through suppression of CD44s and the ERK1/2 pathway
| العنوان: | Tunicamycin inhibits cell proliferation and migration in hepatocellular carcinoma through suppression of CD44s and the ERK1/2 pathway |
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| المؤلفون: | Hong Li, Chao Ge, Helei Hou, Hua Tian, Jinjun Li, Hefen Sun |
| المصدر: | Cancer Science |
| بيانات النشر: | John Wiley and Sons Inc., 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, MAPK/ERK pathway, Cancer Research, Cell cycle checkpoint, Carcinoma, Hepatocellular, MAP Kinase Signaling System, Antineoplastic Agents, Apoptosis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cell, Molecular, and Stem Cell Biology, Cell Movement, Transforming Growth Factor beta, Cell Line, Tumor, Humans, Cell Proliferation, biology, ERK1/2, Chemistry, Cell growth, Tunicamycin, CD44, Liver Neoplasms, EMT, Cell migration, General Medicine, Transforming growth factor beta, Original Articles, hepatocellular carcinoma, Cell Cycle Checkpoints, Cadherins, digestive system diseases, G2 Phase Cell Cycle Checkpoints, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Hyaluronan Receptors, Oncology, 030220 oncology & carcinogenesis, biology.protein, Cancer research, CD44s, Original Article, Mitogen-Activated Protein Kinases, Signal Transduction |
| الوصف: | Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated. In our previous studies, we found that TM reversed drug resistance and improved the efficacy of combination treatments for hepatocellular carcinomas (HCC). Here, we investigated the effects of TM on HCC cell proliferation and migration as well as the mechanism of those effects. Our results showed that TM inhibited cell proliferation and migration as well as induced apoptosis of hepatocellular carcinoma cells. TM inhibited proliferation of HCC cells by inducing cell apoptosis and cell cycle arrest at the G2/M phase. Meanwhile, TM inhibited migration of HCC cells by suppressing CD44s-mediated epithelial-mesenchymal transition (EMT). TM inhibited migration and invasion of HCC cells by decreasing CD44 expression and altering its glycosylation. In addition, CD44s is involved in promoting EMT and is associated with a poor prognosis in HCC patients. Overexpression of CD44s promoted tumor migration and activated phosphorylation of ERK1/2 in HCC cells, whereas TM inhibited CD44s overexpression-associated cell migration. The ability of TM to inhibit cell migration and invasion was enhanced or reversed in CD44s knockdown cells and cells overexpressing CD44s, respectively. The MEK/ERK inhibitor U0126 and TM inhibited hyaluronic acid-induced cell migration in HCC cells. Furthermore, TM inhibited exogenous transforming growth factor beta (TGF-β)-mediated EMT by an ERK1/2-dependent mechanism and restored the TGF-β-mediated loss of E-cadherin. In summary, our study provides evidence that TM inhibits proliferation and migration of HCC cells through inhibition of CD44s and the ERK1/2 signaling pathway. |
| اللغة: | English |
| تدمد: | 1349-7006 1347-9032 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c8decd3d1504a58077040bf999c8d64Test http://europepmc.org/articles/PMC5891198Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1c8decd3d1504a58077040bf999c8d64 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13497006 13479032 |
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