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 language | English |
|---|---|
| Pages (from-to) | 1750-1760 |
| Number of pages | 11 |
| Journal | Cell Death and Differentiation |
| Volume | 19 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 2012 |
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Keywords
- 3D culture
- basal layer of epithelium
- basement membrane
- microRNA
- p63
- prostate cancer
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
Cite this
MiR-205 regulates basement membrane deposition in human prostate : Implications for cancer development. / 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.
In: Cell Death and Differentiation, Vol. 19, No. 11, 11.2012, p. 1750-1760.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MiR-205 regulates basement membrane deposition in human prostate
T2 - Implications for cancer development
AU - Gandellini, P.
AU - Profumo, V.
AU - Casamichele, A.
AU - Fenderico, N.
AU - Borrelli, S.
AU - Petrovich, G.
AU - Santilli, G.
AU - Callari, M.
AU - Colecchia, M.
AU - Pozzi, S.
AU - De Cesare, M.
AU - Folini, M.
AU - Valdagni, R.
AU - Mantovani, R.
AU - Zaffaroni, N.
PY - 2012/11
Y1 - 2012/11
N2 - 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.
AB - 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.
KW - 3D culture
KW - basal layer of epithelium
KW - basement membrane
KW - microRNA
KW - p63
KW - prostate cancer
UR - http://www.scopus.com/inward/record.url?scp=84871003536&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84871003536&partnerID=8YFLogxK
U2 - 10.1038/cdd.2012.56
DO - 10.1038/cdd.2012.56
M3 - Article
C2 - 22555458
AN - SCOPUS:84871003536
VL - 19
SP - 1750
EP - 1760
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
SN - 1350-9047
IS - 11
ER -