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Title: | EMT and induction of miR-21 mediate metastasis development in Trp53-deficient tumours |
Author: | 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. |
Keywords: | Metàstasi Tumors Micro RNAs Metastasis MicroRNAs |
Issue Date: | 31-May-2012 |
Publisher: | Nature Publishing Group |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/srep00434 |
It is part of: | Scientific Reports, 2012, vol. 2 |
URI: | http://hdl.handle.net/2445/126524 |
Related resource: | https://doi.org/10.1038/srep00434 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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