title: A therapeutic approach to treat prostate cancer by targeting Nm23-H1/h-Prune interaction.
abstract: Nm23-H1 is a metastasis suppressor gene whose overexpression is associated with both reduced cell motility in various cancers and increased metastatic potential in neuroblastomas, osteosarcomas, and hematological malignances. We previously reported that Nm23-H1 exerts tumor suppressor action in prostate cancer cells and that h-Prune, which is overexpressed in various tumor types, binds Nm23-H1. Moreover, blockage of the Nm23-H1/h-Prune interaction with a competitive permeable peptide (CPP) attenuates migration of breast and neuroblastoma cells. This series of events suggests that the Nm23-H1/h-Prune protein complex regulates cancer progression and that its specific impairment could be a new therapeutic strategy in oncology. We found that CPP leads to inhibition of the AKT/mTORv and NF-kBv signaling pathways and also activates apoptosis. To obtain a proof-of-concept of our hypothesis, we used a xenograft model of prostate cancer to evaluate whether impairment of this complex using CPP results in an anti-tumoral effect. Using a mouse orthotopic model with bioluminescent imaging, we show evidences that CPP reduces prostate cancer metastases formation. In conclusion, CPP being able to impair formation of the h-Prune/Nm23-H1 complex holds promise for the treatment of prostate cancer.
authors.affiliation: Centro di Ingegneria Genetica e Biotecnologia Avanzate (CEINGE), Naples, Italy.
authors.forename: Marianeve
authors.initials: M
authors.lastname: Carotenuto
authors.forename: Pasqualino
authors.initials: P
authors.lastname: de Antonellis
authors.forename: Cristina Maria
authors.initials: CM
authors.lastname: Chiarolla
authors.forename: Carmela
authors.initials: C
authors.lastname: Attanasio
authors.forename: Valentina
authors.initials: V
authors.lastname: Damiani
authors.forename: Iolanda
authors.initials: I
authors.lastname: Boffa
authors.forename: Nadia
authors.initials: N
authors.lastname: Aiese
authors.forename: Emilia
authors.initials: E
authors.lastname: Pedone
authors.forename: Benedetta
authors.initials: B
authors.lastname: Accordi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Luigi
authors.initials: L
authors.lastname: Navas
authors.forename: Ciro
authors.initials: C
authors.lastname: Imbimbo
authors.forename: Massimo
authors.initials: M
authors.lastname: Zollo
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D057846:Cell-Penetrating Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D054778:NM23 Nucleoside Diphosphate Kinases