Abstract
Toll‐like receptor 4 (TLR4) plays an essential role in cancer progress. Here, we find that the expression of TLR4 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 TLR4 in cancer stemness. We reported that TLR4‐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 CD133+ CD49f+ population and side population, enhanced sphere formation, and the upregulation of stemness marker gene‐SOX2. Downregulation of SOX2 attenuated the enhanced HCC stemness induced by LPS, indicating SOX2 as a downstream mediator of LPS‐TLR4 signaling. The role of LPS‐TLR4 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.
Highlights
Hepatocellular carcinoma (HCC) is a major problem that challenges human health worldwide.[1,2] In China, hepatocellular carcinoma (HCC) is one of leading causes of cancer‐associated death.[3]
These findings suggest that enhanced protein expression levels of Toll‐like receptor 4 (TLR4) and SOX2 are associated with the relapse of HCC
We found that heptoma cell lines expressed relatively higher level of TLR4 at both mRNA and protein levels when compared with L02, a human liver cell line
Summary
Hepatocellular carcinoma (HCC) is a major problem that challenges human health worldwide.[1,2] In China, HCC is one of leading causes of cancer‐associated death.[3] the treatments for HCC are effective at the early stage. Most of HCCs are detected at advanced stage when traditional chemotherapy has limited effects, which causes poor prognosis. Relapse of HCC is a big problem after surgical resection and liver transplantation.[4,5] Because of its poor outcome, mechanistic study of HCC and identification of novel therapeutic target are urgently needed
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