Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma
Year: 2017
Type: article
Abstract: 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.
Source: Nature Communications
Authors: Jose Mario Gonzalez-Meljem, Scott Haston, Gabriela Carreno, John R. Apps, Sara Pozzi, Christina Stache, Grace Kaushal, Alex Virasami, Leonidas Panousopoulos, Seyedeh Neda Mousavy-Gharavy, Ana Guerrero, Mamunur Rashid, Nital Jani, Colin R. Goding, Thomas S. Jacques, David J. Adams, Jesus Gil, Cynthia L. Andoniadou, Juan Pedro Martinez-Barbera
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,560
Funders: Wellcome Trust, NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research, Cancer Research UK, National Institute for Health and Care Research, University College London, CHILDREN with CANCER UK, Consejo Nacional de Ciencia y Tecnología, Great Ormond Street Hospital for Children, University of California, Los Angeles, Medical Research Council, National Cancer Institute
OpenAlex ID: W2768478289