EMT and induction of miR-21 mediate metastasis development in Trp53-deficient tumours

Missense mutations in TP53 gene promote metastasis in human tumours. However, little is known about the complete loss of function of p53 in tumour metastasis. Here we show that squamous cell carcinomas generated by the specific ablation of Trp53 gene in mouse epidermis are highly metastatic. Biochem...

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Detalles Bibliográficos
Autores: Bornachea, Olga, Santos, Mirentxu, Martínez Cruz, Ana Belén, García Escudero, Ramón, Dueñas, Marta, Costa, Clotilde, Segrelles, Carmen, Lorz, Corina, Buitrago, Agueda, Saiz Ladera, Cristina, Agirre, Xabier, Grande, Teresa, Paradela, Beatriz, Maraver, Antonio, Ariza, José M., Prosper, Felipe, Serrano Marugán, Manuel, Sánchez Céspedes, Montserrat, Paramio, Jesús M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/126524
Acceso en línea:https://hdl.handle.net/2445/126524
Access Level:acceso abierto
Palabra clave:Metàstasi
Tumors
Micro RNAs
Metastasis
MicroRNAs
Descripción
Sumario:Missense mutations in TP53 gene promote metastasis in human tumours. However, little is known about the complete loss of function of p53 in tumour metastasis. Here we show that squamous cell carcinomas generated by the specific ablation of Trp53 gene in mouse epidermis are highly metastatic. Biochemical and genome-wide mRNA and miRNA analyses demonstrated that metastases are associated with the early induction of epithelial-mesenchymal transition (EMT) and deregulated miRNA expression in primary tumours. Increased expression of miR-21 was observed in undifferentiated, prometastatic mouse tumours and in human tumours characterized by p53 mutations and distant metastasis. The augmented expression of miR-21, mediated by active mTOR and Stat3 signalling, conferred increased invasive properties to mouse keratinocytes in vitro and in vivo, whereas blockade of miR-21 in a metastatic spindle cell line inhibits metastasis development. Collectively these data identify novel molecular mechanisms leading to metastasis in vivo originated by p53 loss in epithelia.

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