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.
|Titolo:||miR-205 regulates basement membrane deposition in human prostate: implications for cancer development|
MANTOVANI, ROBERTO (Penultimo)
|Parole Chiave:||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|
|Settore Scientifico Disciplinare:||Settore BIO/18 - Genetica|
|Data di pubblicazione:||nov-2012|
|Digital Object Identifier (DOI):||10.1038/cdd.2012.56|
|Appare nelle tipologie:||01 - Articolo su periodico|