AUTHOR=Sharma Ankush , Cinti Caterina , Capobianco Enrico 

TITLE=Multitype Network-Guided Target Controllability in Phenotypically Characterized Osteosarcoma: Role of Tumor Microenvironment

JOURNAL=Frontiers in Immunology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00918

DOI=10.3389/fimmu.2017.00918

ISSN=1664-3224

ABSTRACT=This study highlights the relevance of network-guided controllability analysis as a precision oncology tool. Target controllability through networks is potentially relevant to cancer research for the identification of therapeutic targets. With reference to a recent study on multiple phenotypes from 22 Osteosarcoma cell lines characterized both in vitro and in vivo, we found that a variety of critical proteins in OS regulation circuits were in part phenotype-specific and in part shared. To generalize our inference approach and match cancer phenotypic heterogeneity, we employed multitype networks and identified targets in correspondence with protein sub-complexes. Therefore, we established the relevance for diagnostic and therapeutic purposes of inspecting interactive targets, namely those enriched by significant connectivity patterns in protein sub-complexes. Emerging targets appeared with reference to the OS microenvironment, and relatively to SLRP members and D-type cyclins, among other collagen, laminin and keratin proteins. These described were evidences shared across all phenotypes; instead, specific evidences were provided by critical proteins included IGFBP7 and PDGFRA in the invasive phenotype, and FGFR3 and THBS1 in the colony forming phenotype.