title: ΔNp63α expression induces loss of cell adhesion in triple-negative breast cancer cells.
abstract: p63, a member of the p53 protein family, plays key roles in epithelial development and carcinogenesis. In breast cancer, p63 expression has been found predominantly in basal-A (epithelial-type) triple-negative breast carcinomas (TNBC). To investigate the functional role of p63 in basal-A TNBC, we created MDA-MB-468 cell lines with inducible expression of the two major N-terminal p63 isoforms, TAp63α and ∆Np63α.
  
  
  
  TAp63α did not have significant effect on gene expression profile and cell phenotype, whilst the main effect of ΔNp63α was reduction of cell adhesion. Gene expression profiling revealed genes involved in cell adhesion and migration whose expression relies on overexpression of ΔNp63α. Reduced cell adhesion also led to decreased cell proliferation in vitro and in vivo. Similar data were obtained in another basal-A cell line, BT-20, but not in BT-549 basal-B (mesenchymal-like) TNBC cells.
  
  
  
  In basal-A TNBC cells, ∆Np63α has much stronger effects on gene expression than TAp63α. Although p63 is mentioned mostly in connection with breast cell differentiation and stem cell regulation, we showed that a major effect of p63 is regulation of cell adhesion, a process important in metastasis and invasion of tumour cells. That this effect is not seen in mesenchymal-type TNBC cells suggests lineage-dependent functions, mirroring the expression of ∆Np63α in primary human breast cancers.
authors.affiliation: Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, 65653, Czech Republic.
authors.forename: Marta
authors.initials: M
authors.lastname: Nekulova
authors.affiliation: Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, 65653, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Holcakova
authors.affiliation: Department of Medical Biosciences, Umeå University, Umeå, 90185, Sweden.
authors.forename: Xiaolian
authors.initials: X
authors.lastname: Gu
authors.affiliation: Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, 65653, Czech Republic.
authors.forename: Vaclav
authors.initials: V
authors.lastname: Hrabal
authors.affiliation: Institute of Biology, Medicinal Chemistry & Biotechnology, NHRF, Athens, Greece.
authors.forename: Sotiris
authors.initials: S
authors.lastname: Galtsidis
authors.affiliation: Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, 65653, Czech Republic.
authors.forename: Paulina
authors.initials: P
authors.lastname: Orzol
authors.affiliation: NCRC, 026-329S, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Biology, Medicinal Chemistry & Biotechnology, NHRF, Athens, Greece.
authors.forename: Stella
authors.initials: S
authors.lastname: Logotheti
authors.affiliation: Institute of Biology, Medicinal Chemistry & Biotechnology, NHRF, Athens, Greece.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Zoumpourlis
authors.affiliation: Department of Medical Biosciences, Umeå University, Umeå, 90185, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Nylander
authors.affiliation: Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, 65653, Czech Republic.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Coates
authors.affiliation: Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, 65653, Czech Republic. vojtesek@mou.cz.
authors.forename: Borivoj
authors.initials: B
authors.lastname: Vojtesek
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D064593:Heterografts; D006801:Humans; D020033:Protein Isoforms; D014157:Transcription Factors / Q000235:genetics*; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D020033:Protein Isoforms; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
keywords: Adhesion; Triple-negative breast cancer; p63 isoforms