Enhanced myeloid differentiation factor 88 promotes tumor metastasis via induction of epithelial–mesenchymal transition in human hepatocellular carcinoma
| Autor: | Wu Gb, Yajun Guo, Jing Zhao, Lei Zhang, Xiaoyu Fan, Yuanzhou Zhang, Rongjie Jia, Xuyu Zhou, Guo Sw, Huajing Wang, Lei Cao, Rui Chen, Wei Jing, Minhui Zhu |
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| Rok vydání: | 2014 |
| Předmět: |
Male
0301 basic medicine Cancer Research Time Factors Kaplan-Meier Estimate Mice SCID epithelial–mesenchymal transition Metastasis Glycogen Synthase Kinase 3 Mice 0302 clinical medicine Phosphorylation Mice Inbred BALB C Liver Neoplasms Hep G2 Cells Prognosis Up-Regulation Class Ia Phosphatidylinositol 3-Kinase 030220 oncology & carcinogenesis Hepatocellular carcinoma RNA Interference Original Article Signal Transduction Carcinoma Hepatocellular Epithelial-Mesenchymal Transition Thymoma Immunology Mice Nude Biology Transfection 03 medical and health sciences Cellular and Molecular Neuroscience Biomarkers Tumor medicine Animals Humans Epithelial–mesenchymal transition Protein kinase B PI3K/AKT/mTOR pathway Glycogen Synthase Kinase 3 beta tumor metastasis myeloid differentiation factor 88 Cell Biology medicine.disease digestive system diseases Enzyme Activation 030104 developmental biology Cancer research Myeloid Differentiation Factor 88 Snail Family Transcription Factors Proto-Oncogene Proteins c-akt Transcription Factors |
| Zdroj: | Cell Death & Disease |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/cddis.2014.71 |
| Popis: | Metastasis is the leading cause of death in patients with hepatocellular carcinoma (HCC) after curative resection. Therefore, it is critical to understand the mechanisms underlying tumor metastasis in HCC. We have previously shown that elevated expression of myeloid differentiation factor 88 (MyD88) may promote tumor growth and metastasis in HCC. In this study, we reported that enhanced expression of MyD88 promoted epithelial–mesenchymal transition (EMT) properties and tumor-initiating capabilities in HCC cells. MyD88 was found to be able to interact with p85, a regulatory subunit of phosphoinositide 3-kinase (PI3-K), independent of TLR/IL-1R-mediated response and caused PI3-K/v-akt murine thymoma viral oncogene homolog (Akt) activation, which resulted in subsequent phosphorylation of glycogen synthase kinase-3β and stabilization of Snail, a critical EMT mediator. Consistently, we observed a significant correlation between MyD88 expression and p-Akt levels in a cohort of HCC patients, and found that the combination of these two parameters have better prognostic value for HCC patients. Taken together, these results suggest that elevated MyD88 may facilitate HCC metastasis by promoting EMT properties and tumor-initiating capabilities via PI3–K/Akt pathway. |
| Databáze: | OpenAIRE |
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