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Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma
Senescent cells may promote tumour progression through the activation of a senescence-associated secretory phenotype (SASP), whether these cells are capable of initiating tumourigenesis in vivo is not known. Expression of oncogenic β-catenin in Sox2+ young adult pituitary stem cells leads to formati...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703905/ https://www.ncbi.nlm.nih.gov/pubmed/29180744 http://dx.doi.org/10.1038/s41467-017-01992-5 |
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author | Gonzalez-Meljem, Jose Mario Haston, Scott Carreno, Gabriela Apps, John R. Pozzi, Sara Stache, Christina Kaushal, Grace Virasami, Alex Panousopoulos, Leonidas Mousavy-Gharavy, Seyedeh Neda Guerrero, Ana Rashid, Mamunur Jani, Nital Goding, Colin R. Jacques, Thomas S. Adams, David J. Gil, Jesus Andoniadou, Cynthia L. Martinez-Barbera, Juan Pedro |
author_facet | Gonzalez-Meljem, Jose Mario Haston, Scott Carreno, Gabriela Apps, John R. Pozzi, Sara Stache, Christina Kaushal, Grace Virasami, Alex Panousopoulos, Leonidas Mousavy-Gharavy, Seyedeh Neda Guerrero, Ana Rashid, Mamunur Jani, Nital Goding, Colin R. Jacques, Thomas S. Adams, David J. Gil, Jesus Andoniadou, Cynthia L. Martinez-Barbera, Juan Pedro |
author_sort | Gonzalez-Meljem, Jose Mario |
collection | PubMed |
description | Senescent cells may promote tumour progression through the activation of a senescence-associated secretory phenotype (SASP), whether these cells are capable of initiating tumourigenesis in vivo is not known. Expression of oncogenic β-catenin in Sox2+ young adult pituitary stem cells leads to formation of clusters of stem cells and induction of tumours resembling human adamantinomatous craniopharyngioma (ACP), derived from Sox2− cells in a paracrine manner. Here, we uncover the mechanisms underlying this paracrine tumourigenesis. We show that expression of oncogenic β-catenin in Hesx1+ embryonic precursors also results in stem cell clusters and paracrine tumours. We reveal that human and mouse clusters are analogous and share a common signature of senescence and SASP. Finally, we show that mice with reduced senescence and SASP responses exhibit decreased tumour-inducing potential. Together, we provide evidence that senescence and a stem cell-associated SASP drive cell transformation and tumour initiation in vivo in an age-dependent fashion. |
format | Online Article Text |
id | pubmed-5703905 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57039052017-11-30 Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma Gonzalez-Meljem, Jose Mario Haston, Scott Carreno, Gabriela Apps, John R. Pozzi, Sara Stache, Christina Kaushal, Grace Virasami, Alex Panousopoulos, Leonidas Mousavy-Gharavy, Seyedeh Neda Guerrero, Ana Rashid, Mamunur Jani, Nital Goding, Colin R. Jacques, Thomas S. Adams, David J. Gil, Jesus Andoniadou, Cynthia L. Martinez-Barbera, Juan Pedro Nat Commun Article Senescent cells may promote tumour progression through the activation of a senescence-associated secretory phenotype (SASP), whether these cells are capable of initiating tumourigenesis in vivo is not known. Expression of oncogenic β-catenin in Sox2+ young adult pituitary stem cells leads to formation of clusters of stem cells and induction of tumours resembling human adamantinomatous craniopharyngioma (ACP), derived from Sox2− cells in a paracrine manner. Here, we uncover the mechanisms underlying this paracrine tumourigenesis. We show that expression of oncogenic β-catenin in Hesx1+ embryonic precursors also results in stem cell clusters and paracrine tumours. We reveal that human and mouse clusters are analogous and share a common signature of senescence and SASP. Finally, we show that mice with reduced senescence and SASP responses exhibit decreased tumour-inducing potential. Together, we provide evidence that senescence and a stem cell-associated SASP drive cell transformation and tumour initiation in vivo in an age-dependent fashion. Nature Publishing Group UK 2017-11-28 /pmc/articles/PMC5703905/ /pubmed/29180744 http://dx.doi.org/10.1038/s41467-017-01992-5 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Gonzalez-Meljem, Jose Mario Haston, Scott Carreno, Gabriela Apps, John R. Pozzi, Sara Stache, Christina Kaushal, Grace Virasami, Alex Panousopoulos, Leonidas Mousavy-Gharavy, Seyedeh Neda Guerrero, Ana Rashid, Mamunur Jani, Nital Goding, Colin R. Jacques, Thomas S. Adams, David J. Gil, Jesus Andoniadou, Cynthia L. Martinez-Barbera, Juan Pedro Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma |
title | Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma |
title_full | Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma |
title_fullStr | Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma |
title_full_unstemmed | Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma |
title_short | Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma |
title_sort | stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703905/ https://www.ncbi.nlm.nih.gov/pubmed/29180744 http://dx.doi.org/10.1038/s41467-017-01992-5 |
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