Specific variations in YTHDF1 expression were detected in YTHDF1-overexpressing, -knockout, and -knockdown human hepatocellular carcinoma (HCC) cells, HCC organoids, and HCC patient-derived xenograft murine models.
[Signal Transduction and Targeted Therapy]
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Li, Q., Ni, Y., Zhang, L., Jiang, R., Xu, J., Yang, H., Hu, Y., Qiu, J., Pu, L., Tang, J., & Wang, X. (2021). HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation. Signal Transduction and Targeted Therapy, 6(1), 1–13. https://doi.org/10.1038/s41392-020-00453-8 Cite
Scientists revealed that activation of the Hypoxia Inducible Factor-2 (HIF2α) due to deficiency of HIF-prolyl hydroxylase domain protein-2 boosts neutrophil migration specifically through highly confined microenvironments.
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Sormendi, S., Deygas, M., Sinha, A., Bernard, M. L. M., Krüger, A., Koutzelis, I., Le Lay, G. M., Sáez, P. J., Gerlach, M., Franke, K., Meneses, A., Kräter, M., Palladini, A., Guck, J., Coskun, Ü., Chavakis, T., Vargas, P., & Wielockx, B. (2021). HIF2α is a Direct Regulator of Neutrophil Motility. Blood, blood.2020007505. https://doi.org/10.1182/blood.2020007505 Cite
Researchers undertook experiments to define structural determinants of hypoxia-inducible factor that potentiate antitumor efficacy in cytotoxic T cells.
[Cancer Immunology Research]
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Researchers demonstrated that in non-human primates, amylin deposition in heart failure contributed to cardiac dysfunction via activation of HIF1α and PFKFB3 signaling.
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ERO1 alpha deficiency reduced tumor cell migration and lung metastases by impinging on tumor angiogenesis, negatively regulating the upstream ATF4/CHOP branch of the Unfolded Protein Response and selectively impeding oxidative folding of angiogenic factors, among which VEGF-A.
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Varone, E., Decio, A., Chernorudskiy, A., Minoli, L., Brunelli, L., Ioli, F., Piotti, A., Pastorelli, R., Fratelli, M., Gobbi, M., Giavazzi, R., & Zito, E. (2021). The ER stress response mediator ERO1 triggers cancer metastasis by favoring the angiogenic switch in hypoxic conditions. Oncogene, 1–16. https://doi.org/10.1038/s41388-021-01659-y Cite
Human peripheral blood-derived endothelial progenitor cells were cultured under microgravity (MG) or normal gravity (NG) followed by analysis for angiogenic gene expression. Furthermore, the serum-free cultured medium under MG or NG were collected, and their pro-angiogenic properties were examined in HUVECs.
[Current Stem Cell Research & Therapy]
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Kong, L., Wang, Y., Wang, H., Pan, Q., Zuo, R., Bai, S., Zhang, X., Lee, W. Y., Kang, Q., & Li, G. (2021). Conditioned media from endothelial progenitor cells cultured in simulated microgravity promote angiogenesis and bone fracture healing. Stem Cell Research & Therapy, 12(1), 47. https://doi.org/10.1186/s13287-020-02074-y Cite
Scientists generated human cancer cell lines of pancreatic and lung origin carrying an inducible shRNA against NRF2 and PERK. They report that PERK-related phosphorylation of NRF2 was only critical in Keap1 wildtype cells to escape its degradation, but showed no direct effect on nuclear import or transcriptional activity of NRF2.
[Cell Death & Disease]
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Küper, A., Baumann, J., Göpelt, K., Baumann, M., Sänger, C., Metzen, E., Kranz, P., & Brockmeier, U. (2021). Overcoming hypoxia-induced resistance of pancreatic and lung tumor cells by disrupting the PERK-NRF2-HIF-axis. Cell Death & Disease, 12(1), 1–11. https://doi.org/10.1038/s41419-020-03319-7 Cite
The authors investigated molecular mechanisms that altered the growth and metabolism of isolated lymphatic endothelial cells exposed to prolonged pathologically elevated lymph flow in vivo within the anatomic and physiologic context of a large animal model of congenital heart disease with increased pulmonary blood flow using in vitro approaches.
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Boehme, J. T., Morris, C. J., Chiacchia, S. R., Gong, W., Wu, K. Y., Kameny, R. J., Raff, G. W., Fineman, J. R., Maltepe, E., & Datar, S. A. (2021). HIF-1α promotes cellular growth in lymphatic endothelial cells exposed to chronically elevated pulmonary lymph flow. Scientific Reports, 11(1), 1468. https://doi.org/10.1038/s41598-020-80882-1 Cite
Researchers assessed miR-675-3p-related regulatory mechanisms in melanoma and the clinical relevance of such regulatory activities.
Researchers report that under hypoxic conditions, alternative splicing of MBD2 was suppressed, favoring the production of MBD2a which facilitated breast cancer metastasis.
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Liu, Z., Sun, L., Cai, Y., Shen, S., Zhang, T., Wang, N., Wu, G., Ma, W., Li, S.-T., Suo, C., Hao, Y., Jia, W.-D., Semenza, G. L., Gao, P., & Zhang, H. (2021). Hypoxia-induced suppression of alternative splicing of MBD2 promotes breast cancer metastasis via activation of FZD1. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-20-2876 Cite
The authors outline the role of LOX-1 in tumor spreading and metastasis, evidencing its function in VEGF induction, HIF-1alpha activation, and MMP-9/MMP-2 expression, pushing up the neoangiogenic and the epithelial-mesenchymal transition process in glioblastoma, osteosarcoma, prostate, colon, breast, lung, and pancreatic tumors.
[Cancer Gene Therapy]