Article (Scientific journals)
ΔNp63α expression induces loss of cell adhesion in triple-negative breast cancer cells
Nekulova, M.; Holcakova, J.; Gu, X. et al.
2016In BMC Cancer, 16 (1)
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Keywords :
Adhesion; P63 isoforms; Triple-negative breast cancer; TP63 protein, human; Article; Animals; Cell Adhesion; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cells, Cultured; Disease Models, Animal; Female; Gene Expression; Gene Expression Profiling; Heterografts; Humans; Protein Isoforms; Transcription Factors; Triple Negative Breast Neoplasms; Tumor Suppressor Proteins
Abstract :
[en] Background: 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 ΔNp63α. Results: 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. Conclusions: In basal-A TNBC cells, ΔNp63α 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 ΔNp63α in primary human breast cancers. © 2016 The Author(s).
Disciplines :
Biochemistry, biophysics & molecular biology
Identifiers :
eid=2-s2.0-84990852841
Author, co-author :
Nekulova, M.;  Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic
Holcakova, J.;  Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic
Gu, X.;  Department of Medical Biosciences, Umeå University, Umeå, Sweden
Hrabal, V.;  Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic
Galtsidis, Sotirios ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Orzol, P.;  Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic
Liu, Y.;  NCRC, 026-329S, University of Michigan, Ann Arbor, MI, United States
Logotheti, S.;  Institute of Biology, Medicinal Chemistry and Biotechnology, NHRF, Athens, Greece
Zoumpourlis, V.;  Institute of Biology, Medicinal Chemistry and Biotechnology, NHRF, Athens, Greece
Nylander, K.;  Department of Medical Biosciences, Umeå University, Umeå, Sweden
Coates, P. J.;  Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic
Vojtesek, B.;  Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic
External co-authors :
yes
Language :
English
Title :
ΔNp63α expression induces loss of cell adhesion in triple-negative breast cancer cells
Publication date :
2016
Journal title :
BMC Cancer
ISSN :
1471-2407
Publisher :
BioMed Central Ltd.
Volume :
16
Issue :
1
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 07 November 2017

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