| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2093493 | Stem Cell Reports | 2015 | 15 Pages |
•ANXA3 potentiates cancer and stem cell-like properties in CD133+ liver CSCs•ANXA3 is internalized via caveolae-mediated endocytosis and activates the JNK pathway•A novel neutralizing anti-ANXA3 antibody is developed•ANXA3 is a novel biomarker for HCC diagnosis
SummaryFrequent tumor relapse in hepatocellular carcinoma (HCC) has been commonly attributed to the presence of residual cancer stem cells (CSCs) after conventional treatments. We have previously identified and characterized CD133 to mark a specific CSC subset in HCC. In the present study, we found endogenous and secretory annexin A3 (ANXA3) to play pivotal roles in promoting cancer and stem cell-like features in CD133+ liver CSCs through a dysregulated JNK pathway. Blockade of ANXA3 with an anti-ANXA3 monoclonal antibody in vitro as well as in human HCC xenograft models resulted in a significant reduction in tumor growth and self-renewal. Clinically, ANXA3 expression in HCC patient sera closely associated with aggressive clinical features. Our results suggest that ANXA3 can serve as a novel diagnostic biomarker and that the inhibition of ANXA3 may be a viable therapeutic option for the treatment of CD133+ liver-CSC-driven HCC.
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