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The Immune Receptor Tim-3 Mediates Activation of PI3 kinase/mTOR and HIF-1 Pathways in Human Myeloid Leukaemia Cells

Prokhorov, Alexandr, Gibbs, Bernhard F., Bardelli, Marco, Rüegg, Laura, Fasler-Kan, Elizaveta, Varani, Luca, Sumbayev, Vadim V. (2015) The Immune Receptor Tim-3 Mediates Activation of PI3 kinase/mTOR and HIF-1 Pathways in Human Myeloid Leukaemia Cells. International Journal of Biochemistry and Cell Biology, 59 . pp. 11-20. ISSN 1357-2725. E-ISSN 1878-5875. (doi:10.1016/j.biocel.2014.11.017) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1016/j.biocel.2014.11.017

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 mediates growth factor type responses in acute myeloid leukaemia cells by triggering 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 finding suggest that Tim-3 could be used as a potential therapeutic target for immune therapy and drug delivery in human acute myeloid leukaemia cells.

Item Type: Article
DOI/Identification number: 10.1016/j.biocel.2014.11.017
Projects: [UNSPECIFIED] EAACI Research Fellowship
[UNSPECIFIED] Specific Targeting of mTOR-HIF-1 Pathways in Human Acute Myeloid Leukaemia Cells
Subjects: Q Science > QP Physiology (Living systems) > QP506 Molecular biology
Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Q Science > QR Microbiology > QR180 Immunology
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Bernhard F. Gibbs
Date Deposited: 02 Dec 2014 17:22 UTC
Last Modified: 29 May 2019 13:49 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/45700 (The current URI for this page, for reference purposes)
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