Liver cancer stem cells (LCSCs) indicating that IL-8 signaling is crucial for the conservation of stemness features of cancer cells.All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/306910 doi: bioRxiv preprint first posted online Apr. 25, 2018; 3 Conclusion: PI3K/Akt/mTOR pathway inhibitors alter hepatic CSC composition and gene expression in favor or to the detriment of cancer stem cell survival. Blockade of IL-8 signaling provides a promising therapeutic approach for prevention of LCSC enrichment.Keywords: Hepatocellular carcinoma, Liver cancer stem cells, Sorafenib, PI3K/AKT pathway, interleukin 8All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/306910 doi: bioRxiv preprint first posted online Apr. 25, 2018; 4
Introductory StatementHepatocellular carcinoma (HCC) is the second common cause of cancer mortality and the fifth most common malignancy in human cancers (1) .Chronic liver injury is caused by viral diseases, exposure to chemicals, and other environmental or autoimmune conditions which constitute the risk factors for HCC (2, 3). Liver cancer is known to originate from hepatic progenitor cells (HPC) during cirrhosis and has a very heterogeneous histological structure. In this process, HPCs are damaged and transformed to liver cancer stem cells (LCSCs) which are responsible for chemoresistance, tumor relapse and metastasis (4). Sorafenib and Regorafenib are multikinase inhibitors, which are the only clinical treatment options for advanced HCC patients approved by Markers validated for the identification of LCSCs include CD133, EpCAM, CD90, CD44, CD24, CD13, and OV6 as well as Hoechst dye efflux or aldehyde dehydrogenase (ALDH) activity (7). In our previous study, it was well defined that CD133 and EpCAM were convenient to detect LCSCs of epithelial like (well-differentiated) cells, whereas CD90 was efficient to detect LCSCs of mesenchymal like (poorly differentiated) cells (8, 9).We report here that the small molecule inhibitor Rapamycin inhibits the enrichment of LCSCs and regulates pathways related with stemness. Additionally, gene expression analysis along with pathway scoring results have revealed several potential targets such as IL-8 against cancer stem cell enrichment, where blockade of IL-8 pathway was shown to prevent enrichment of LCSC population significantly.All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/306910 doi: bioRxiv preprint first posted online Apr. 25, 2018; 5
Experimental Pro...