期刊
FEBS LETTERS
卷 589, 期 8, 页码 897-903出版社
WILEY
DOI: 10.1016/j.febslet.2015.02.026
关键词
Msi1; Tumor necrosis factor-related apoptosis-inducing ligand; Drug resistance; Hepatocellular carcinoma; ERK
资金
- National Science and Technology Major Project [2009ZX10004-312]
- National Natural Science Foundation of China [81271885]
- Program for New Century Excellent Talents in University [NCET-09-0339]
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. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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