title: Prostate cancer regulatory networks.
abstract: Although the timing with which common epithelial malignancies arise and become established remains a matter of debate, it is clear that by the time they are detected these tumors harbor hundreds of deregulated, aberrantly expressed or mutated genes. This enormous complexity poses formidable challenges to identify gene pathways that are drivers of tumorigenesis, potentially suitable for therapeutic intervention. An alternative approach is to consider cancer pathways as interconnected networks, and search for potential nodal proteins capable of connecting multiple signaling networks of tumor maintenance. We have modeled this approach in advanced prostate cancer, a condition with current limited therapeutic options. We propose that the integration of three signaling networks, including chaperone-mediated mitochondrial homeostasis, integrin-dependent cell signaling, and Runx2-regulated gene expression in the metastatic bone microenvironment plays a critical role in prostate cancer maintenance, and offers novel options for molecular therapy.
authors.affiliation: Department of Cancer Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA. dario.altieri@umassmed.edu
authors.forename: Dario C
authors.initials: DC
authors.lastname: Altieri
authors.forename: Lucia R
authors.initials: LR
authors.lastname: Languino
authors.forename: Jane B
authors.initials: JB
authors.lastname: Lian
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stein
authors.forename: Irwin
authors.initials: I
authors.lastname: Leav
authors.forename: Andre J
authors.initials: AJ
authors.lastname: van Wijnen
authors.forename: Zhong
authors.initials: Z
authors.lastname: Jiang
authors.forename: Gary S
authors.initials: GS
authors.lastname: Stein
mesh_terms: D055808:Drug Discovery; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D015398:Signal Transduction
chemical_list: D039564:Integrin alphaV