title: Proteomic analysis of human Sonic Hedgehog (SHH) medulloblastoma stem-like cells.
abstract: Human medulloblastoma (MB) is a malignant brain tumor that comprises four distinct molecular subgroups including the Sonic Hedgehog (SHH)-MB group. A leading cause of the SHH subgroup is an aberrant activation of the SHH pathway, a developmental signaling that regulates postnatal development of the cerebellum by promoting the mitotic expansion of granule neural precursors (GNPs) in the external granule layer (EGL). The abnormal SHH signaling pathway drives not only SHH-MB but also its cancer stem-like cells (SLCs), which represent a fraction of the tumor cell population that maintain cancer growth and have been associated with high grade tumors. Here, we report the first proteomic analysis of human SHH-MB SLCs before and after Retinoic Acid (RA)-induced differentiation. A total of 994 nLC-MS buckets were statistically analysed returning 68 modulated proteins between SLCs and their differentiated counterparts. Heat Shock Protein 70 (Hsp70) was one of the proteins that characterized the protein profile of SLCs. By means of Ingenuity Pathway Analysis (IPA), Genomatix analysis and extending the network obtained using the differentially expressed proteins we found a correlation between Hsp70 and the NF-κB complex. A key driver of the SHH-MB group is cMET whose downstream proliferation/survival signalling is indeed via PI3K/Akt/NF-κB. We confirmed the results of the proteomic analysis by western blot, underlining that a P-p65/NF-κB activatory complex is highly expressed in SLCs. Taking together these results we define a new protein feature of SHH-MB SLCs.
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ronci
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Catanzaro
authors.forename: Luisa
authors.initials: L
authors.lastname: Pieroni
authors.forename: Agnese
authors.initials: A
authors.lastname: Po
authors.forename: Zein Mersini
authors.initials: ZM
authors.lastname: Besharat
authors.forename: Viviana
authors.initials: V
authors.lastname: Greco
authors.forename: Stefano
authors.initials: S
authors.lastname: Levi Mortera
authors.forename: Isabella
authors.initials: I
authors.lastname: Screpanti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferretti
authors.forename: Andrea
authors.initials: A
authors.lastname: Urbani
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008527:Medulloblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020543:Proteome / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics; D015398:Signal Transduction; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D020543:Proteome; C509239:SHH protein, human; D014212:Tretinoin