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

• DOI: 10.1038/srep00434
• Publication Date: 2012-05-31T09:04:55Z
• Authors: Olga Bornachea; Mirentxu Santos; Ana Belén Martíne...; Ramón García-Escu...; Marta Dueñas; Clotilde Costa; Carmen Segrelles; Corina Lorz; Agueda Buitrago; Cristina Saiz-Ladera; Xabier Agirre; Teresa Grande; Beatriz Paradela; Antonio Maraver; José M. Ariza; Felipe Prosper; Manuel Serrano; Montse Sánchez-Cé...; Jesús M. Paramio
• Keywords: Keratinocytes; STAT3 Transcription Factor; 0301 basic medicine; Micro RNAs; Epithelial-Mesenchymal Transition; Lung Neoplasms; Blotting, Western; Kaplan-Meier Estimate; Article; Metastasis; Cell Line; Mice; 03 medical and health sciences; Metàstasi; Animals; Humans; Neoplasm Metastasis; Cells, Cultured; Tumors; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; Gene Expression Profiling; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; Mutation; Carcinoma, Squamous Cell; Epidermis

Missense mutations in TP53 gene promote metastasis human tumours. However, little is known about the complete loss of function p53 tumour metastasis. Here we show that squamous cell carcinomas generated by specific ablation Trp53 mouse epidermis are highly metastatic. Biochemical and genome-wide mRNA miRNA analyses demonstrated metastases associated with early induction epithelial-mesenchymal transition (EMT) deregulated expression primary Increased miR-21 was observed undifferentiated, prometastatic tumours characterized distant The augmented miR-21, mediated active mTOR Stat3 signalling, conferred increased invasive properties to keratinocytes vitro vivo, whereas blockade a metastatic spindle line inhibits development. Collectively these data identify novel molecular mechanisms leading vivo originated epithelia.