IL-7R-mediated signaling in T-cell acute lymphoblastic leukemia: An update
| Autor: | João T. Barata, Daniel Dias Ribeiro, Padma Akkapeddi, Mariana L. Oliveira, Alice Melão |
|---|---|
| Přispěvatelé: | Repositório da Universidade de Lisboa |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Cancer Research Cell Survival T cell Interleukin 7 Biology Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Article B-cell acute lymphoblastic leukemia Interleukin-7 Receptor alpha Subunit 03 medical and health sciences 0302 clinical medicine JAK/STAT pathway Genetics medicine Animals Humans Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Severe combined immunodeficiency Cell Cycle JAK-STAT signaling pathway IL-7R medicine.disease PI3K/Akt/mTOR pathway Neoplasm Proteins Leukemia 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Molecular Medicine T-ALL T-cell acute lymphoblastic leukemia Signal Transduction Lymphoid leukemia |
| Zdroj: | Advances in Biological Regulation |
| ISSN: | 2212-4926 |
| DOI: | 10.1016/j.jbior.2018.09.012 |
| Popis: | © 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/) Interleukin 7 (IL-7) and its receptor (IL-7R, a heterodimer of IL-7Rα and γc) are essential for normal lymphoid development. In their absence, severe combined immunodeficiency occurs. By contrast, excessive IL-7/IL-7R-mediated signaling can drive lymphoid leukemia development, disease acceleration and resistance to chemotherapy. IL-7 and IL-7R activate three main pathways: STAT5, PI3K/Akt/mTOR and MEK/Erk, ultimately leading to the promotion of leukemia cell viability, cell cycle progression and growth. However, the contribution of each of these pathways towards particular functional outcomes is still not completely known and appears to differ between normal and malignant states. For example, IL-7 upregulates Bcl-2 in a PI3K/Akt/mTOR-dependent and STAT5-independent manner in T-ALL cells. This is a 'symmetric image' of what apparently happens in normal lymphoid cells, where PI3K/Akt/mTOR does not impact on Bcl-2 and regulates proliferation rather than survival. In this review, we provide an updated summary of the knowledge on IL-7/IL-7R-mediated signaling in the context of cancer, focusing mainly on T-cell acute lymphoblastic leukemia, where this axis has been more extensively studied. Publication costs were supported by LISBOA-01-0145-FEDER-007391, project cofunded by FEDER, through POR Lisboa2020 Programa Operacional Regional de Lisboa, PORTUGAL 2020, and Fundação para a Ciência e a Tecnologia (FCT, Portugal). The research work in JTB's lab related to the present review was supported by the grants FAPESP/20015/2014 and PTDC/MEC-HEM/31588/2017, from FCT; and by the consolidator grant ERC CoG-648455 from the European Research Council, under the European Union's Horizon 2020 research and innovation programme. JTB is an FCT investigator (consolidator). MLO is a LisbonBioMed PhD student and received a fellowship from FCT. PA received a PhD fellowship from the EU Marie Sklodowska-Curie ITN Protein Conjugates. |
| Databáze: | OpenAIRE |
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