P63 regulates tubular formation via epithelial-to-mesenchymal transition

Y. Zhang, W. Yan, Xinbin Chen

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

P63, a p53 family member, is expressed as TA and ΔN isoforms. Interestingly, both TAp63 and ΔNp63 are transcription factors, and regulate both common and distinct sets of target genes. p63 is required for survival of some epithelial cell lineages, and lack of p63 leads to loss of epidermis and other epithelia in humans and mice. Here, we explored the role of p63 isoforms in cell proliferation, migration and tubulogenesis by using Madin-Darby Canine Kidney (MDCK) tubular epithelial cells in two-or three-dimensional (2-D or 3-D) culture. We found that like downregulation of p53, downregulation of p63 and TAp63 decreases expression of growth-suppressing genes, including p21, PUMA and MIC-1, and consequently promotes cell proliferation and migration in 2-D culture. However, in 3-D culture, downregulation of p63, especially TAp63, but not p53, decapacitates MDCK cells to form a cyst structure through enhanced epithelial-to-mesenchymal transition (EMT). In contrast, downregulation of ΔNp63 inhibits MDCK cell proliferation and migration in 2-D culture, and delays but does not block MDCK cell cyst formation and tubulogenesis in 3-D culture. Consistent with this, downregulation of ΔNp63 markedly upregulates growth-suppressing genes, including p21, PUMA and MIC-1. Taken together, these data suggest that TAp63 is the major isoform required for tubulogenesis by maintaining an appropriate level of EMT, whereas ΔNp63 fine-tunes the rate of cyst formation and tubulogenesis by maintaining an appropriate expression level of genes involved in cell cycle arrest and apoptosis.

Original languageEnglish (US)
Pages (from-to)1548-1557
Number of pages10
JournalOncogene
Volume33
Issue number12
DOIs
StatePublished - Mar 20 2014

Fingerprint

Epithelial-Mesenchymal Transition
Down-Regulation
Madin Darby Canine Kidney Cells
Cell Movement
Cysts
Protein Isoforms
Cell Proliferation
Epithelial Cells
Genes
Cell Lineage
Growth
Cell Cycle Checkpoints
Epidermis
Canidae
Transcription Factors
Up-Regulation
Epithelium
Apoptosis
Kidney
Gene Expression

Keywords

  • Cell proliferation
  • Epithelial-to-mesenchymal transition
  • Migration and invasion
  • P63
  • The p53 family
  • Tubular formation

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

P63 regulates tubular formation via epithelial-to-mesenchymal transition. / Zhang, Y.; Yan, W.; Chen, Xinbin.

In: Oncogene, Vol. 33, No. 12, 20.03.2014, p. 1548-1557.

Research output: Contribution to journalArticle

Zhang, Y. ; Yan, W. ; Chen, Xinbin. / P63 regulates tubular formation via epithelial-to-mesenchymal transition. In: Oncogene. 2014 ; Vol. 33, No. 12. pp. 1548-1557.
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