Investigating senescence in cellular plasticity and tissue regeneration
Cellular senescence has mainly been associated with tumor suppression and aging, mediated through cell intrinsic cell-cycle inhibition and arrest. However, through secretion of specific proteins, termed the senescence-associated secretory phenotype (SASP), senescent cells can have paradoxical effect...
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| Formato: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2017 |
| País: | España |
| Recursos: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/481989 |
| Acesso em linha: | http://hdl.handle.net/10803/481989 |
| Access Level: | acceso abierto |
| Palavra-chave: | Senescence Plasticity Stem cells Papilloma SASP Senescencia Plasticidad celular Célula madre Papiloma 576 |
| Resumo: | Cellular senescence has mainly been associated with tumor suppression and aging, mediated through cell intrinsic cell-cycle inhibition and arrest. However, through secretion of specific proteins, termed the senescence-associated secretory phenotype (SASP), senescent cells can have paradoxical effects, promoting proliferation, invasion or paracrine senescence in neighbouring cells. Additionally, emerging studies showed that cellular senescence is also implicated in complex biological processes such as embryonic development, tissue repair and wound healing. Unexpectedly, we found that primary mouse keratinocytes undergoing oncogene-induced senescence exhibit an increase in stem cell gene expression. Interestingly, this signature can also be induced in normal cells upon transient exposure to the SASP. However, prolonged exposure to the SASP leads to paracrine senescence in vitro as a possible mechanism to counteract the aberrant regenerative stimulation. Together this work suggests that the SASP is a regenerative mechanism that instructs stemness and plasticity, but if left unperturbed can have detrimental effects seen during aging and tumor formation. |
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