Investigators showed that histone lysine demethylase 4D (JMJD2D) expression was increased in liver cancer stem-like cells (LCSCs); downregulation of JMJD2D inhibited the self-renewal of LCSCs in vitro and in vivo and inhibited the lung metastasis of LCSCs by reducing the survival and the early lung seeding of circulating LCSCs.
[Journal of Biological Chemistry]
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Deng, Y., Li, M., Zhuo, M., Guo, P., Chen, Q., Mo, P., Li, W., & Yu, C. (2020). Histone demethylase JMJD2D promotes the self-renewal of liver cancer stem-like cells by enhancing EpCAM and Sox9 expression. Journal of Biological Chemistry, jbc.RA120.015335. https://doi.org/10.1074/jbc.RA120.015335 Cite
PIDDosome deficiency reduced tumor number and burden, despite the inability to activate p53 in polyploid cells. Liver tumors arose primarily from cells with low ploidy, indicating an intrinsic pro‐tumorigenic effect of PIDDosome‐mediated ploidy restriction.
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Sladky, V. C., Knapp, K., Szabo, T. G., Braun, V. Z., Bongiovanni, L., van den Bos, H., Spierings, D. C., Westendorp, B., Curinha, A., Stojakovic, T., Scharnagl, H., Timelthaler, G., Tsuchia, K., Pinter, M., Semmler, G., Foijer, F., de Bruin, A., Reiberger, T., Rohr-Udilova, N., & Villunger, A. (2020). PIDDosome-induced p53-dependent ploidy restriction facilitates hepatocarcinogenesis. EMBO Reports, n/a(n/a), e50893. https://doi.org/10.15252/embr.202050893 Cite
Investigators summarize and highlight the role of these cells in liver cancer and propose strategies to therapeutically target them. They also discuss current immunotherapeutic strategies in hepatocellular carcinoma and outline recent advances in our understanding of how the therapeutic potential of these agents might be enhanced.
[Cellular & Molecular Immunology]
Ablation of REGγ increased the stability of protein phosphatase 2 catalytic subunit in vitro and in vivo, which dephosphorylated AKT1 substrate 1 and stabilized the interaction between PRAS40 and Raptor to inactive mTORC1-mediated hyper-glycolytic metabolism.
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Yao, L., Xuan, Y., Zhang, H., Yang, B., Ma, X., Wang, T., Meng, T., Sun, W., Wei, H., Ma, X., Moses, R., Xiao, J., Zhang, P., Ge, C., Li, J., Li, L., Li, X., Li, J., & Zhang, B. (2020). Reciprocal REGγ-mTORC1 regulation promotes glycolytic metabolism in hepatocellular carcinoma. Oncogene, 1–16. https://doi.org/10.1038/s41388-020-01558-8 Cite
Lower levels of P450 family 2 subfamily C member 8 (CYP2C8) were confirmed in liver cancer cells. CYP2C8 overexpression efficiently attenuated liver cancer cell proliferation and promoted apoptosis.
[Cancer Biology & Therapy]
Researchers showed by genetic lineage tracing that PROM1+ cells were derived in part from hepatocytes in alcoholic hepatitis and became tumor cells in mice with diethyl nitrosamine-initiated, Western alcohol diet-promoted liver tumorigenesis.
Surface Oncology develop next-generation immunotherapies that target the tumor microenvironment. They have announced that the US FDA has granted Fast Track designation to SRF388 for the treatment of patients with hepatocellular carcinoma, or liver cancer, who have been previously treated with standard therapies, such as vascular endothelial growth factor targeted agents and programmed death-ligand blockade.
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Currently, neutrophils, with their autocrine, paracrine, and immune modulation functions, have been shown to be involved in liver diseases, including viral hepatitis, nonalcoholic steatohepatitis, alcoholic liver disease, liver fibrosis, cirrhosis, liver failure, and liver cancer. Accordingly, this review summarizes the role of neutrophils in liver diseases.
[Cellular & Molecular Immunology]
Human hepatocellular carcinoma (HCC) cell lines and HCC mouse models were used to assess the therapeutic efficacy and targeted molecular pathways of cabozantinib, either alone or in combination with the pan-mTOR inhibitor MLN0128 or the checkpoint inhibitor anti-PD-L1 antibody.
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Shang, R., Song, X., Wang, P., Zhou, Y., Lu, X., Wang, J., Xu, M., Chen, X., Utpatel, K., Che, L., Liang, B., Cigliano, A., Evert, M., Calvisi, D. F., & Chen, X. (2020). Cabozantinib-based combination therapy for the treatment of hepatocellular carcinoma. Gut. https://doi.org/10.1136/gutjnl-2020-320716 Cite
The fibrotic liver is characterized by the pathological accumulation of ECM proteins. Type VI collagen alpha3 is a biomarker of hepatic fibrosis, and its cleaved form, endotrophin (ETP), plays a critical role in adipose tissue dysfunction, insulin resistance, and breast cancer development. Scientists studied the effects of the Col6a3-derived peptide ETP on the progression of chronic liver diseases, such as NASH and liver cancer.
[Experimental and Molecular Medicine]
Scientists verified that Ether-à-go-go-1 (EAG1) promoted the proliferation of hepatocellular carcinoma both in vitro and in vivo. It promoted cell cycle progression by inhibiting the ubiquitination of SKP2.
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