The downregulation of ΔNp63 in p53-deficient mouse epidermal tumors favors metastatic behavior

• DOI: 10.18632/oncotarget.4353
• Publication Date: 2015-09-16T17:47:25Z
• Authors: Olga Bornachea; Fernando F. López...; Marta Dueñas; Carmen Segrelles; Corina Lorz; Cristian Suárez-C...; María Marañón; Beatriz Paradela-...; Mirentxu Santos; Jesús M. Paramio
• Keywords: Keratinocytes; 0301 basic medicine; Epithelial-Mesenchymal Transition; Skin Neoplasms; Stem Cells; Down-Regulation; Phosphoproteins; Immunohistochemistry; Cell Line; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; Microscopy, Fluorescence; Mutation; Trans-Activators; Animals; Humans; Point Mutation; Epidermis; Neoplasm Metastasis; Skin; Transcription Factors

// Olga Bornachea 1 , Fernando F. López-Calderón 1, 2 Marta Dueñas Carmen Segrelles Corina Lorz Cristian Suárez-Cabrera María Marañón Beatriz Paradela-Dobarro Mirentxu Santos Jesús M. Paramio Molecular Oncology Unit, CIEMAT, 28040 Madrid, Spain Oncology, Institute of Biomedical Investigation University Hospital, 28041 Correspondence to: Santos, e-mail: [e-mail] Paramio, [e-mail] Keywords: p63, p53, metastasis, miRNA, skin Received: May 05, 2015 Accepted: June 19, Published: July 01, ABSTRACT The TP63 gene codes for two major isoform types, TAp63 and ΔNp63, with probable opposite roles in tumorigenesis. ΔNp63α protein is frequently amplified overexpressed different epithelial tumors. Accordingly, it has been considered a potential oncogene. Nonetheless, possible metastatic suppressor activity also suggested based on the experimental observation that its expression reduced or even absent advanced invasive Such activities are often related to tumors bearing point mutated TP53 gene. However, TP53-deficient poorly characterized. Here we show spontaneous tumors, induced by epidermal-specific Trp53 ablation, reduction ΔNp63 an early event, whereas re-expressed lung lesions. Using knock down ectopic approaches, opposes epithelial-mesenchymal transition reduces cells. This process occurs through modulation ΔNp63-dependent downstream targets (including transcription factors microRNAs) likely play roles. Further, favors involved iPS reprogramming, thus suggesting can modulate specific stem cell traits mouse epidermal tumor Overall, our data assign antimetastatic context p53 deficiency epidermis.