RGD Reference Report - Enhanced myeloid differentiation factor 88 promotes tumor metastasis via induction of epithelial-mesenchymal transition in human hepatocellular carcinoma.

General

Enhanced myeloid differentiation factor 88 promotes tumor metastasis via induction of epithelial-mesenchymal transition in human hepatocellular carcinoma.
Authors:	Jia, R-J Cao, L Zhang, L Jing, W Chen, R Zhu, M-H Guo, S-W Wu, G-B Fan, X-Y Wang, H Zhang, Y-Y Zhou, X-Y Zhao, J Guo, Y-J
Citation:	Jia RJ, etal., Cell Death Dis. 2014 Mar 6;5:e1103. doi: 10.1038/cddis.2014.71.
RGD ID:	150530285
Pubmed:	PMID:24603331 (View Abstract at PubMed)
PMCID:	PMC3973199 (View Article at PubMed Central)
DOI:	DOI:10.1038/cddis.2014.71 (Journal Full-text)
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.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
hepatocellular carcinoma	exacerbates	IMP		150530285	human gene and cell in a mouse model	RGD
hepatocellular carcinoma	exacerbates	ISO	MYD88 (Homo sapiens)	150530285; 150530285	human gene and cell in a mouse model	RGD

Objects Annotated

Genes (Rattus norvegicus)

Myd88 (MYD88, innate immune signal transduction adaptor)

Genes (Mus musculus)

Myd88 (myeloid differentiation primary response gene 88)

Genes (Homo sapiens)

MYD88 (MYD88 innate immune signal transduction adaptor)

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Enhanced myeloid differentiation factor 88 promotes tumor metastasis via induction of epithelial-mesenchymal transition in human hepatocellular carcinoma.