The DOI matches its Crossref record; 27 of the 28 references it cites were found in a registry or an index.
Loss of p63 and its microRNA-205 target results in enhanced cell migration and metastasis in prostate cancer
Open accessAbstract
p63 inhibits metastasis. Here, we show that p63 (both TAp63 and ΔNp63 isoforms) regulates expression of miR-205 in prostate cancer (PCa) cells, and miR-205 is essential for the inhibitory effects of p63 on markers of epithelial-mesenchymal transition (EMT), such as ZEB1 and vimentin. Correspondingly, the inhibitory effect of p63 on EMT markers and cell migration is reverted by anti-miR-205. p53 mutants inhibit expression of both p63 and miR-205, and the cell migration, in a cell line expressing endogenous mutated p53, can be abrogated by pre-miR-205 or silencing of mutated p53. In accordance with this in vitro data, ΔNp63 or miR-205 significantly inhibits the incidence of lung metastasis in vivo in a mouse tail vein model. Similarly, one or both components of the p63/miR-205 axis were absent in metastases or colonized lymph nodes in a set of 218 human prostate cancer samples. This was confirmed in an independent clinical data set of 281 patients. Loss of this axis was associated with higher Gleason scores, an increased likelihood of metastatic and infiltration events, and worse prognosis. These data suggest that p63/miR-205 may be a useful clinical predictor of metastatic behavior in prostate cancer.
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“we inhibited p63 and PTEN expression, two genes that are described as tumor-suppressors that play a key role in breast and prostate tissue development (32–35).”
From Direct transfection of clonal organoids in Matrigel microbeads: a promising approach toward organoid-based genetic screens (2018) · cites this paper as [34]
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Muller, P. A. J., & Vousden, K. H. (2013) · Nature Cell Biology · doi:10.1038/ncb2641 · Cited by 1,647
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Self-citation
Metadata
- Authors
- Tucci, P., Agostini, M., Grespi, F., Markert, E. K., Terrinoni, A., Vousden, K. H., Muller, P. A. J., Dötsch, V., Kehrloesser, S., Sayan, B. S., Giaccone, G., Lowe, S. W., Takahashi, N., Vandenabeele, P., Knight, R. A., Levine, A. J., & Melino, G.
- Affiliations
- University of Leicester (GB)
- Institute for Advanced Study (US)
- University of Rome Tor Vergata (IT)
- Cancer Research UK Scotland Institute (GB)
- Goethe University Frankfurt (DE)
- University of Southampton (GB)
- National Institutes of Health (US)
- Memorial Sloan Kettering Cancer Center (US)
- Vlaams Instituut voor Biotechnologie (BE)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-09-04
- Volume
- 109
- Issue
- 38
- Pages
- 15312-15317
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3458363
- OpenAlex
- W2113645544
- Cited by
- 286
- References
- 28
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 11 · 2023: 14 · 2022: 12 · 2021: 20 · 2020: 17 · 2019: 15 · 2018: 18 · 2017: 19 · 2016: 37 · 2015: 30 · 2014: 41 · 2013: 36 · 2012: 6
- FWCI
- 12.00
- Type
- journal article
- Language
- en
- Update notices
- correction (2014-01-17)
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Salford Institutional Repository (University of Salford) (submittedVersion, cc-by)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Durham Research Online (Durham University) (submittedVersion, cc-by)
- Archive of Doctoral Theses and Digital Collections (University of Calabria) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- Ministero della Salute
- Vlaams Instituut voor Biotechnologie
- Associazione Italiana per la Ricerca sul Cancro (2008-2010_33-08)
- Vlaamse regering
- Alleanza Contro il Cancro
- Medical Research Council (ACC12)
- National Cancer Institute (P01CA087497, P01CA87497.)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- p63, miR-205, prostate cancer, metastasis, cell migration, epithelial-mesenchymal transition, ZEB1, vimentin, TP53 mutation, ΔNp63, TAp63, lung metastasis, lymph node metastasis, Gleason score, prognostic factors
- MeSH terms
- Animals, Cell Movement, Humans, Male, Mice, Inbred BALB C, Mutation, Neoplasm Metastasis, Neoplasm Transplantation, Phosphoproteins, Prostatic Neoplasms, Transcription Factors, Biomarkers, Tumor, Trans-Activators, Gene Expression Regulation, Neoplastic, Protein Isoforms, Gene Expression Profiling, Tumor Suppressor Proteins, MicroRNAs, Cell Line, Tumor, Cell Proliferation, Mice, Epithelial-Mesenchymal Transition
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