Msi1 confers resistance to TRAIL by activating ERK in liver cancer cells

descriptionPublicationkeyboard_double_arrow_right Article 03 Mar 2015 English Publisher:WileyJournal:FEBS Letters, volume 589, pages 897-903 (issn: 0014-5793, eissn: 1873-3468,

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Authors: Liu, Nianli; Chen, Tianran; Wang, Xiaohong; Yang, Darong; Xue, Binbin; Zhu, Haizhen;

doi: 10.1016/j.febslet.2015.02.026

pmid: 25747387

Msi1 confers resistance to TRAIL by activating ERK in liver cancer cells

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Abstract

To investigate TRAIL resistance mechanisms in hepatocellular carcinoma (HCC), we isolated a stable TRAIL‐resistant sub‐population of the HCC cell line LH86, designated LH86‐TR. Differential activation of AKT was not responsible for acquisition of TRAIL resistance. Cells with both congenital and acquired resistance to TRAIL exhibited increased Msi1 expression, which conferred TRAIL resistance by activating ERK. Forced expression of Msi1 decreased the sensitivity of HCC cells to TRAIL both in vitro and in vivo. Conversely, shRNA‐mediated depletion of Msi1 enhanced TRAIL efficacy. SiRNA‐mediated depletion of ERK overcame TRAIL resistance. Hence, we conclude that Msi1 is a mediator of TRAIL resistance in HCC cells.

Related Organizations

Central South University
China (People's Republic of)
Hunan Women'S University
China (People's Republic of)

Keywords

Msi1, Carcinoma, Hepatocellular, Hepatocellular carcinoma, Cell Survival, MAP Kinase Signaling System, Apoptosis, Nerve Tissue Proteins, Tumor necrosis factor-related apoptosis-inducing ligand, TNF-Related Apoptosis-Inducing Ligand, Cell Line, Tumor, Biomarkers, Tumor, Humans, Extracellular Signal-Regulated MAP Kinases, Protein Kinase Inhibitors, Liver Neoplasms, RNA-Binding Proteins, Enzyme Activation, Gene Expression Regulation, Neoplastic, ERK, Drug Resistance, Neoplasm, Drug resistance, Neoplastic Stem Cells

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