MiR-205 regulates basement membrane deposition in human prostate: Implications for cancer development

P. Gandellini, V. Profumo, A. Casamichele, N. Fenderico, S. Borrelli, G. Petrovich, G. Santilli, M. Callari, M. Colecchia, S. Pozzi, M. De Cesare, M. Folini, R. Valdagni, R. Mantovani, N. Zaffaroni

Research output: Contribution to journalArticle

Abstract

The basement membrane (BM) is a layer of specialized extracellular matrix that surrounds normal prostate glands and preserves tissue integrity. Lack or discontinuity of the BM is a prerequisite for tumor cell invasion into interstitial spaces, thus favoring metastasis. Therefore, BM maintenance represents a barrier against cancer development and progression. In the study, we show that miR-205 participates in a network involving ΔNp63α, which is essential for maintenance of the BM in prostate epithelium. At the molecular level, ΔNp63α is able to enhance miR-205 transcription by binding to its promoter, whereas the microRNA can post-transcriptionally limit the amount of ΔNp63α protein, mostly by affecting ΔNp63α proteasomal degradation rather than through a canonical miRNA/target interaction. Functionally, miR-205 is able to control the deposition of laminin-332 and its receptor integrin-β4. Hence, pathological loss of miR-205, as widely observed in prostate cancer, may favor tumorigenesis by creating discontinuities in the BM. Here we demonstrate that therapeutic replacement of miR-205 in prostate cancer (PCa) cells can restore BM deposition and 3D organization into normal-like acinar structures, thus hampering cancer progression.

Original languageEnglish
Pages (from-to)1750-1760
Number of pages11
JournalCell Death and Differentiation
Volume19
Issue number11
DOIs
Publication statusPublished - Nov 2012

    Fingerprint

Keywords

  • 3D culture
  • basal layer of epithelium
  • basement membrane
  • microRNA
  • p63
  • prostate cancer

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Gandellini, P., Profumo, V., Casamichele, A., Fenderico, N., Borrelli, S., Petrovich, G., Santilli, G., Callari, M., Colecchia, M., Pozzi, S., De Cesare, M., Folini, M., Valdagni, R., Mantovani, R., & Zaffaroni, N. (2012). MiR-205 regulates basement membrane deposition in human prostate: Implications for cancer development. Cell Death and Differentiation, 19(11), 1750-1760. https://doi.org/10.1038/cdd.2012.56