title: Emerging from the shade of p53 mutants: N-terminally truncated variants of the p53 family in EMT signaling and cancer progression.
abstract: The prevailing view has been that N-terminally truncated p53 family isoforms (ΔNp53, ΔNp63, and DNp73) predominantly counteract cell cycle arrest and apoptosis. Recent progress in the field extend these well-known functions and place these isoforms in the center of a comprehensive regulatory network controlling major epithelial-to-mesenchymal transition (EMT)-relevant signaling pathways [such as transforming growth factor-β (TGF-β), wingless-int (WNT), insulin-like growth factor (IGF), and signal transducer and activator of transcription (STAT)], microRNAs, and EMT-associated transcription factors that promote invasion, loss of tumor cell polarity, and metastatic behavior in conjunction with a chemoresistant phenotype. These observations add new weight to the concept that currently underappreciated truncated forms of this tumor suppressor family play an equally important role in promoting cancer aggressiveness as do mutant p53 proteins, and illustrate how the consequences of ΔN/DN expression depend on cellular contexts. The tumor microenvironment contributes to the emergence of these variants, thereby linking inflammation to the activation of the mesenchymal program. In addition, molecular connections between ΔN/DN forms and self-renewal have arisen, suggesting their potential function in the generation of cancer stem cells (CSCs) from bulk tumor cells. These intriguing insights provoke a new understanding of the acquisition of aggressive traits by carcinoma cells in the absence of p53 mutations, and may help direct the development of new therapies for a broad range of cancers.
authors.affiliation: Institute of Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, Schillingallee 69, 18057 Rostock, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Engelmann
authors.affiliation: Institute of Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, Schillingallee 69, 18057 Rostock, Germany. brigitte.puetzer@med.uni-rostock.de.
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Pützer
mesh_terms: D002277:Carcinoma / Q000235:genetics* / Q000503:physiopathology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008954:Models, Biological; D005810:Multigene Family / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53