miR-205 regulates basement membrane deposition in human prostate: implications for cancer development
Articolo
Data di Pubblicazione:
2012
Citazione:
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. - In: CELL DEATH AND DIFFERENTIATION. - ISSN 1350-9047. - 19:11(2012 Nov), pp. 1750-1760. [10.1038/cdd.2012.56]
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Basement Membrane; Cell Adhesion Molecules; Cell Line; Cell Transformation, Neoplastic; Humans; Integrin beta4; Male; MicroRNAs; Promoter Regions, Genetic; Prostate; Transcription Factors; Transcription, Genetic; Tumor Suppressor Proteins
Elenco autori:
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
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