CD44v6+ hepatocellular carcinoma cells maintain cell stemness through the Met/cjun/Nanog signaling pathway

Background and Purpose: Cancer stem cells (CSCs) are a type of cancer cell owning the characteristic of self-renew and differentiation.We hypothesize that the stemness properties in CD44v6+ hepatocellular carcinoma cells (HCC) is promoted via the Met/cjun/Nanog signaling pathway, thus, serves as a valuable target for HCC therapy. Experimental Approach: We use lentiviral shMet and selective Met inhibitor PHA665752 to explore the function of Met/cjun/Nanog axi in CD44v6+ cells. The orthotopic liver xenograft tumor model was used to detect self-renewal ability of CD44v6+ cells. Furthermore, a luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were carried out to find the exact binding site of cjun in the Nanog promoter. Key Results: In this study, we demonstrated that CD44v6+ CSCs not only facilitate the properties of cancer stemness, but also represent the high expression of the HGF/MET signal pathway. Inhibiting the activation of Met in CD44v6+ HCC cells in vidvo and in vitro significantly decrease the expression of cjun and Nanog. Furthermore, we found a binding site of cjun in 1700bp before the transcription start site of Nanog. Conclusion and Implications: The stemness properties of CD44v6+ cells is promoted by the Met/cjun/Nanog signaling pathway. And the cjun is binding in 1700bp before the transcription start site of Nanog. KEYWORDS：Hepatocellular Carcinoma, Cancer Stem Cells, HGF/MET, CD44v6, cjun