title: miR-205 regulates basement membrane deposition in human prostate: implications for cancer development.
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.
authors.affiliation: Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Gandellini
authors.forename: V
authors.initials: V
authors.lastname: Profumo
authors.forename: A
authors.initials: A
authors.lastname: Casamichele
authors.forename: N
authors.initials: N
authors.lastname: Fenderico
authors.forename: S
authors.initials: S
authors.lastname: Borrelli
authors.forename: G
authors.initials: G
authors.lastname: Petrovich
authors.forename: G
authors.initials: G
authors.lastname: Santilli
authors.forename: M
authors.initials: M
authors.lastname: Callari
authors.forename: M
authors.initials: M
authors.lastname: Colecchia
authors.forename: S
authors.initials: S
authors.lastname: Pozzi
authors.forename: M
authors.initials: M
authors.lastname: De Cesare
authors.forename: M
authors.initials: M
authors.lastname: Folini
authors.forename: R
authors.initials: R
authors.lastname: Valdagni
authors.forename: R
authors.initials: R
authors.lastname: Mantovani
authors.forename: N
authors.initials: N
authors.lastname: Zaffaroni
mesh_terms: D001485:Basement Membrane / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D006801:Humans; D039663:Integrin beta4 / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D039663:Integrin beta4; D035683:MicroRNAs; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000097794:Kalinin; C534425:MIR205, human; C115051:TP63 protein, human