title: DeltaNp63α protein triggers epithelial-mesenchymal transition and confers stem cell properties in normal human keratinocytes.
abstract: p63 is a p53 family protein required for morphogenesis and postnatal regeneration of epithelial tissues. Here we demonstrate that ΔNp63α, a p63 isoform lacking the N-terminal transactivation domain, induces epithelial-mesenchymal transition (EMT) in primary human keratinocytes in a TGF-β-dependent manner. Rapidly proliferating normal human epidermal keratinocytes (NHEK) were infected with retroviral vector expressing ΔNp63α or empty vector and serially subcultured until replicative senescence. No phenotypic changes were observed until the culture reached senescence. Then the ΔNp63α-transduced cells underwent morphological changes resembling mesenchymal cells and acquired the EMT phenotype. Treatment with exogenous TGF-β accelerated EMT in presenescent ΔNp63α-transduced cells, whereas the inhibition of TGF-β signaling reversed the EMT phenotype. TGF-β treatment alone led to growth arrest in control NHEK with no evidence of EMT, indicating that ΔNp63α altered the cellular response to TGF-β treatment. ΔNp63α-transduced cells acquiring EMT gained the ability to be differentiated to osteo-/odontogenic and adipogenic pathways, resembling mesenchymal stem cells. Furthermore, these cells expressed enhanced levels of Nanog and Lin28, which are transcription factors associated with pluripotency. These data indicate that EMT required ΔNp63α transduction and intact TGF-β signaling in NHEK.
authors: School of Dentistry, UCLA, Los Angeles, California 90095.
authors: Ju-Eun
authors: JE
authors: Oh
authors: School of Dentistry, UCLA, Los Angeles, California 90095; Dental Research Institute, UCLA, Los Angeles, California 90095; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095.
authors: Reuben H
authors: RH
authors: Kim
authors: School of Dentistry, UCLA, Los Angeles, California 90095; Dental Research Institute, UCLA, Los Angeles, California 90095; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095.
authors: Ki-Hyuk
authors: KH
authors: Shin
authors: School of Dentistry, UCLA, Los Angeles, California 90095; Dental Research Institute, UCLA, Los Angeles, California 90095; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095; David Geffen School of Medicine, UCLA, Los Angeles, California 90095.
authors: No-Hee
authors: NH
authors: Park
authors: School of Dentistry, UCLA, Los Angeles, California 90095; Dental Research Institute, UCLA, Los Angeles, California 90095; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095. Electronic address: mkang@dentistry.ucla.edu.
authors: Mo K
authors: MK
authors: Kang
mesh_terms: D002460:Cell Line; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D010641:Phenotype; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000502:physiology*
chemical_list: C115051:TP63 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins