In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 22, No. 7 ( 2018-07), p. 3679-3690
Kurzfassung:
The cell surface antigen CD 90 has recently been established as a promising marker for liver cancer stem cells. This study aimed to investigate potential implications of SHH /Gli signalling in CD 90+ liver cancer stem cells. Correlation of the expression of SHH signalling components and CD 90 in liver cancer cells and clinical tissues, as well as in enriched CD 90+ liver cancer stem cells and the TCGA database, were analysed by quantitative RT ‐ PCR , Western blotting and flow cytometry. Functional analysis was conducted by si RNA ‐mediated CD 90, Gli1 and Gli3 gene knockdown, SHH treatment and application of the JAK 2 inhibitor AZD 1480 and IL 6 neutralizing antibody in CD 90+ liver cancer stem cells, followed by cell proliferation, migration, sphere formation and tumorigenicity assays. CD 90 expression exhibited a high positive correlation with Gli1 and Gli3 in multiple liver cancer cell lines and human cancerous liver tissues, both of which showed a significant increase in liver cancer. Analysis of TCGA data revealed an association of CD 90, Gli1 and Gli3 with a short overall survival and positive correlation between CD 90 expression and Gli3 expression level. The stem cell potentials of CD 90+ 97L liver cancer cells were greatly impaired by Gli1/3 knockdown with si RNA but enhanced by SHH treatment. Application of the JAK 2 inhibitor AZD 1480 and IL 6 neutralizing antibody showed the CD 90 and SHH /Gli‐regulated liver cancer stem cell functions were mediated by the IL 6/ JAK 2/ STAT 3 pathway. The stem cell properties of CD 90+ liver cancer cells are regulated by the downstream SHH /Gli and IL 6/ JAK 2/ STAT 3 signalling pathways.
Materialart:
Online-Ressource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2018.22.issue-7
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2018
ZDB Id:
2076114-4
