Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/126524
EMT and induction of miR-21 mediate metastasis development in Trp53-deficient tumours
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
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.
Matèries
Matèries (anglès)
Citació
Citació
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.. EMT and induction of miR-21 mediate metastasis development in Trp53-deficient tumours. _Scientific Reports_. 2012. Vol. 2. [consulta: 23 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/126524]