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Role of ADAM17 in invasion and migration of CD133-expressing liver cancer stem cells after irradiation

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Title
Role of ADAM17 in invasion and migration of CD133-expressing liver cancer stem cells after irradiation
Author(s)
Hong S.W.; Hur W.; Choi J.E.; Kim J.-H.; Daehee Hwang; Yoon S.K.
Subject
ADAM17, ; Cancer stem cells, ; Hepatocellular carcinoma, ; Migration, ; Radioresistance
Publication Date
2016-04
Journal
ONCOTARGET, v.7, no.17, pp.23482 - 23497
Publisher
IMPACT JOURNALS LLC
Abstract
We investigated the biological role of CD133-expressing liver cancer stem cells (CSCs) enriched after irradiation of Huh7 cells in cell invasion and migration. We also explored whether a disintegrin and metalloproteinase-17 (ADAM17) influences the metastatic potential of CSC-enriched hepatocellular carcinoma (HCC) cells after irradiation. A CD133-expressing Huh7 cell subpopulation showed greater resistance to sublethal irradiation and specifically enhanced cell invasion and migration capabilities. We also demonstrated that the radiation-induced MMP-2 and MMP-9 enzyme activities as well as the secretion of vascular endothelial growth factor were increased more predominantly in Huh7CD133+ cell subpopulations than Huh7CD133- cell subpopulations. Furthermore, we showed that silencing ADAM17 significantly inhibited the migration and invasiveness of enriched Huh7CD133+ cells after irradiation; moreover, Notch signaling was significantly reduced in irradiated CD133-expressing liver CSCs following stable knockdown of the ADAM17 gene. In conclusion, our findings indicate that CD133-expressing liver CSCs have considerable metastatic capabilities after irradiation of HCC cells, and their metastatic capabilities might be maintained by ADAM17. Therefore, suppression of ADAM17 shows promise for improving the efficiency of current radiotherapies and reducing the metastatic potential of liver CSCs during HCC treatment.
URI
https://pr.ibs.re.kr/handle/8788114/2575
DOI
10.18632/oncotarget.8112
ISSN
1949-2553
Appears in Collections:
Center for Plant Aging Research (식물 노화·수명 연구단) > 1. Journal Papers (저널논문)
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