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Msi1 confers resistance to TRAIL by activating ERK in liver cancer cells
Author(s) -
Liu Nianli,
Chen Tianran,
Wang Xiaohong,
Yang Darong,
Xue Binbin,
Zhu Haizhen
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.02.026
Subject(s) - mapk/erk pathway , protein kinase b , cancer research , small hairpin rna , in vivo , hepatocellular carcinoma , in vitro , cell culture , population , medicine , immunology , biology , microbiology and biotechnology , signal transduction , gene knockdown , biochemistry , genetics , environmental health
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.