TLR 4 increases the stemness and is highly expressed in relapsed human hepatocellular carcinoma

Abstract Toll‐like receptor 4 ( TLR 4) plays an essential role in cancer progress. Here, we find that the expression of TLR 4 in relapsed human hepatocellular carcinoma ( HCC ) clinical samples is higher than that in the non‐relapsed ones, which leads us to explore the role of TLR 4 in cancer stemness. We reported that TLR 4‐ AKT signaling pathway was activated by lipopolysaccharides ( LPS ) in HCC cell lines to enhance the cancer stemness capacity, which was reflected by the increased percentage of CD 133 + CD 49f + population and side population, enhanced sphere formation, and the upregulation of stemness marker gene‐ SOX 2 . Downregulation of SOX 2 attenuated the enhanced HCC stemness induced by LPS , indicating SOX 2 as a downstream mediator of LPS ‐ TLR 4 signaling. The role of LPS ‐ TLR 4 signaling in inducing HCC stemness was further confirmed by tumor xenograft experiment in vivo. Taken together, our findings provide a novel therapeutic target to prevent the recurrence of HCC .