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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
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.
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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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