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

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Abstract
p63 inhibits metastasis. Here, we show that p63 (both TAp63 and Delta Np63 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, Delta Np63 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.
Keywords
P53, TUMOR, SUPPRESSOR, MIR-205, INVASION, ZEB1, GROWTH

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Chicago
Tucci, Paola, Massimiliano Agostini, Francesca Grespi, Elke K Markert, Alessandro Terrinoni, Karen H Vousden, Patricia AJ Muller, 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.
APA
Tucci, P., Agostini, M., Grespi, F., Markert, E. K., Terrinoni, A., Vousden, K. H., Muller, P. A., 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.
Vancouver
1.
Tucci P, Agostini M, Grespi F, Markert EK, Terrinoni A, Vousden KH, et al. 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. 2012;109(38):15312–7.
MLA
Tucci, Paola, Massimiliano Agostini, Francesca Grespi, et al. “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 (2012): 15312–15317. Print.
@article{3040507,
  abstract     = {p63 inhibits metastasis. Here, we show that p63 (both TAp63 and Delta Np63 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, Delta Np63 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.},
  author       = {Tucci, Paola and Agostini, Massimiliano and Grespi, Francesca and Markert, Elke K and Terrinoni, Alessandro and Vousden, Karen H and Muller, Patricia AJ and Dötsch, Volker and Kehrloesser, Sebastian and Sayan, Berna S and Giaccone, Giuseppe and Lowe, Scott W and Takahashi, Nozomi and Vandenabeele, Peter and Knight, Richard A and Levine, Arnold J and Melino, Gennaro},
  issn         = {0027-8424},
  journal      = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
  keywords     = {P53,TUMOR,SUPPRESSOR,MIR-205,INVASION,ZEB1,GROWTH},
  language     = {eng},
  number       = {38},
  pages        = {15312--15317},
  title        = {Loss of p63 and its microRNA-205 target results in enhanced cell migration and metastasis in prostate cancer},
  url          = {http://dx.doi.org/10.1073/pnas.1110977109},
  volume       = {109},
  year         = {2012},
}

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