The immune receptor Tim-3 mediates activation of PI3 kinase/mTOR and HIF-1 pathways in human myeloid leukaemia cells |
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Affiliation: | 1. Pharmacodelivery Group, School of Pharmacy, University College Cork, Ireland;2. Department of Haematology, Cork University Hospital, Ireland;3. Cork Cancer Research Centre, University College Cork, Ireland;1. School of Pharmaceutical Science, Key Laboratory of Chemical Biology (Ministry of Education), Shandong University, Jinan 250012, China;2. School of Biological Science and Technology, University of Jinan, 336 West Road of Nan Xinzhuang, Jinan 250022, China |
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Abstract: | The T-cell immunoglobulin and mucin domain 3 (Tim-3) is a plasma membrane-associated protein that is highly expressed in human acute myeloid leukaemia cells. As an acute myeloid leukaemia antigen, it could therefore be considered as a potential target for immune therapy and highly-specific drug delivery. However, a conceptual understanding of its biological role is required before consideration of this protein for therapeutic settings. Here, we reveal the detailed mechanism of action underlying the biological responses mediated by the Tim-3 receptor in myeloid cells. Our studies demonstrate that Tim-3 triggers growth factor type responses in acute myeloid leukaemia cells by activating a phosphatidylinositol-3 kinase (PI-3K)/mammalian target of rapamycin (mTOR) pathway. In addition, the receptor activates hypoxic signalling pathways upregulating glycolysis and pro-angiogenic responses. These findings suggest that Tim-3 could be used as a potential therapeutic target for immune therapy and drug delivery in human acute myeloid leukaemia cells. |
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Keywords: | Myeloid leukaemia cells Tim-3 Mammalian target of rapamycin (mTOR) pathway HIF-1 |
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