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Transforming growth factor beta type 1 (TGF-β) and hypoxia-inducible factor 1 (HIF-1) transcription complex as master regulators of the immunosuppressive protein galectin-9 expression in human cancer and embryonic cells
Galectin-9 is one of the key proteins employed by a variety of human malignancies to suppress anti-cancer activities of cytotoxic lymphoid cells and thus escape immune surveillance. Human cancer cells in most cases express higher levels of galectin-9 compared to non-transformed cells. However, the b...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762483/ https://www.ncbi.nlm.nih.gov/pubmed/33295886 http://dx.doi.org/10.18632/aging.202343 |
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author | Selnø, Anette Teo Hansen Schlichtner, Stephanie Yasinska, Inna M. Sakhnevych, Svetlana S. Fiedler, Walter Wellbrock, Jasmin Klenova, Elena Pavlova, Ludmila Gibbs, Bernhard F. Degen, Martin Schnyder, Isabelle Aliu, Nijas Berger, Steffen M. Fasler-Kan, Elizaveta Sumbayev, Vadim V. |
author_facet | Selnø, Anette Teo Hansen Schlichtner, Stephanie Yasinska, Inna M. Sakhnevych, Svetlana S. Fiedler, Walter Wellbrock, Jasmin Klenova, Elena Pavlova, Ludmila Gibbs, Bernhard F. Degen, Martin Schnyder, Isabelle Aliu, Nijas Berger, Steffen M. Fasler-Kan, Elizaveta Sumbayev, Vadim V. |
author_sort | Selnø, Anette Teo Hansen |
collection | PubMed |
description | Galectin-9 is one of the key proteins employed by a variety of human malignancies to suppress anti-cancer activities of cytotoxic lymphoid cells and thus escape immune surveillance. Human cancer cells in most cases express higher levels of galectin-9 compared to non-transformed cells. However, the biochemical mechanisms underlying this phenomenon remain unclear. Here we report for the first time that in human cancer as well as embryonic cells, the transcription factors hypoxia-inducible factor 1 (HIF-1) and activator protein 1 (AP-1) are involved in upregulation of transforming growth factor beta 1 (TGF-β1) expression, leading to activation of the transcription factor Smad3 through autocrine action. This process triggers upregulation of galectin-9 expression in both malignant (mainly in breast and colorectal cancer as well as acute myeloid leukaemia (AML)) and embryonic cells. The effect, however, was not observed in mature non-transformed human cells. TGF-β1-activated Smad3 therefore displays differential behaviour in human cancer and embryonic vs non-malignant cells. This study uncovered a self-supporting biochemical mechanism underlying high levels of galectin-9 expression operated by the human cancer and embryonic cells employed in our investigations. Our results suggest the possibility of using the TGF-β1 signalling pathway as a potential highly efficient target for cancer immunotherapy. |
format | Online Article Text |
id | pubmed-7762483 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-77624832021-01-08 Transforming growth factor beta type 1 (TGF-β) and hypoxia-inducible factor 1 (HIF-1) transcription complex as master regulators of the immunosuppressive protein galectin-9 expression in human cancer and embryonic cells Selnø, Anette Teo Hansen Schlichtner, Stephanie Yasinska, Inna M. Sakhnevych, Svetlana S. Fiedler, Walter Wellbrock, Jasmin Klenova, Elena Pavlova, Ludmila Gibbs, Bernhard F. Degen, Martin Schnyder, Isabelle Aliu, Nijas Berger, Steffen M. Fasler-Kan, Elizaveta Sumbayev, Vadim V. Aging (Albany NY) Research Paper Galectin-9 is one of the key proteins employed by a variety of human malignancies to suppress anti-cancer activities of cytotoxic lymphoid cells and thus escape immune surveillance. Human cancer cells in most cases express higher levels of galectin-9 compared to non-transformed cells. However, the biochemical mechanisms underlying this phenomenon remain unclear. Here we report for the first time that in human cancer as well as embryonic cells, the transcription factors hypoxia-inducible factor 1 (HIF-1) and activator protein 1 (AP-1) are involved in upregulation of transforming growth factor beta 1 (TGF-β1) expression, leading to activation of the transcription factor Smad3 through autocrine action. This process triggers upregulation of galectin-9 expression in both malignant (mainly in breast and colorectal cancer as well as acute myeloid leukaemia (AML)) and embryonic cells. The effect, however, was not observed in mature non-transformed human cells. TGF-β1-activated Smad3 therefore displays differential behaviour in human cancer and embryonic vs non-malignant cells. This study uncovered a self-supporting biochemical mechanism underlying high levels of galectin-9 expression operated by the human cancer and embryonic cells employed in our investigations. Our results suggest the possibility of using the TGF-β1 signalling pathway as a potential highly efficient target for cancer immunotherapy. Impact Journals 2020-12-08 /pmc/articles/PMC7762483/ /pubmed/33295886 http://dx.doi.org/10.18632/aging.202343 Text en Copyright: © 2020 Selnø et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Selnø, Anette Teo Hansen Schlichtner, Stephanie Yasinska, Inna M. Sakhnevych, Svetlana S. Fiedler, Walter Wellbrock, Jasmin Klenova, Elena Pavlova, Ludmila Gibbs, Bernhard F. Degen, Martin Schnyder, Isabelle Aliu, Nijas Berger, Steffen M. Fasler-Kan, Elizaveta Sumbayev, Vadim V. Transforming growth factor beta type 1 (TGF-β) and hypoxia-inducible factor 1 (HIF-1) transcription complex as master regulators of the immunosuppressive protein galectin-9 expression in human cancer and embryonic cells |
title | Transforming growth factor beta type 1 (TGF-β) and hypoxia-inducible factor 1 (HIF-1) transcription complex as master regulators of the immunosuppressive protein galectin-9 expression in human cancer and embryonic cells |
title_full | Transforming growth factor beta type 1 (TGF-β) and hypoxia-inducible factor 1 (HIF-1) transcription complex as master regulators of the immunosuppressive protein galectin-9 expression in human cancer and embryonic cells |
title_fullStr | Transforming growth factor beta type 1 (TGF-β) and hypoxia-inducible factor 1 (HIF-1) transcription complex as master regulators of the immunosuppressive protein galectin-9 expression in human cancer and embryonic cells |
title_full_unstemmed | Transforming growth factor beta type 1 (TGF-β) and hypoxia-inducible factor 1 (HIF-1) transcription complex as master regulators of the immunosuppressive protein galectin-9 expression in human cancer and embryonic cells |
title_short | Transforming growth factor beta type 1 (TGF-β) and hypoxia-inducible factor 1 (HIF-1) transcription complex as master regulators of the immunosuppressive protein galectin-9 expression in human cancer and embryonic cells |
title_sort | transforming growth factor beta type 1 (tgf-β) and hypoxia-inducible factor 1 (hif-1) transcription complex as master regulators of the immunosuppressive protein galectin-9 expression in human cancer and embryonic cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762483/ https://www.ncbi.nlm.nih.gov/pubmed/33295886 http://dx.doi.org/10.18632/aging.202343 |
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