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miR-205 regulates basement membrane deposition in human prostate: implications for cancer development.
- Source :
- Cell Death & Differentiation; Nov2012, Vol. 19 Issue 11, p1750-1760, 11p, 1 Color Photograph, 1 Diagram, 6 Graphs
- Publication Year :
- 2012
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13509047
- Volume :
- 19
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- Cell Death & Differentiation
- Publication Type :
- Academic Journal
- Accession number :
- 82336597
- Full Text :
- https://doi.org/10.1038/cdd.2012.56