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.

Tucci, P., Agostini, M., Grespi, F., Markert, E., Terrinoni, A., Vousden, K., et al. (2012). Loss of p63 and its microRNA-205 target results in enhanced cell migration and metastasis in prostate cancer. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 109(38), 15312-15317 [10.1073/pnas.1110977109].

Loss of p63 and its microRNA-205 target results in enhanced cell migration and metastasis in prostate cancer

AGOSTINI, MASSIMILIANO;Terrinoni, A;MELINO, GENNARO
2012-09-18

Abstract

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.
18-set-2012
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/11 - BIOLOGIA MOLECOLARE
English
Cell Movement; Animals; MicroRNAs; Humans; Cell Line, Tumor; Mice; Cell Proliferation; Mice, Inbred BALB C; Protein Isoforms; Tumor Suppressor Proteins; Epithelial-Mesenchymal Transition; Neoplasm Transplantation; Gene Expression Regulation, Neoplastic; Gene Expression Profiling; Transcription Factors; Phosphoproteins; Neoplasm Metastasis; Tumor Markers, Biological; Trans-Activators; Prostatic Neoplasms; Mutation; Male
Tucci, P., Agostini, M., Grespi, F., Markert, E., Terrinoni, A., Vousden, K., et al. (2012). Loss of p63 and its microRNA-205 target results in enhanced cell migration and metastasis in prostate cancer. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 109(38), 15312-15317 [10.1073/pnas.1110977109].
Tucci, P; Agostini, M; Grespi, F; Markert, E; Terrinoni, A; Vousden, K; Muller, P; Dötsch, V; Kehrloesser, S; Sayan, B; Giaccone, G; Lowe, S; Takahas...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/78435
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