title: SOCS1 favors the epithelial-mesenchymal transition in melanoma, promotes tumor progression and prevents antitumor immunity by PD-L1 expression.
abstract: Silencing of SOCS1 protein with shRNAi lentivirus (shR-SOCS1) led to partial reversion of the tumorigenic phenotype of B16F10-Nex2 melanoma cells. SOCS1 silencing inhibited cell migration and invasion as well as in vitro growth by cell cycle arrest at S phase with increased cell size and nuclei. Down-regulation of SOCS1 decreased the expression of epidermal growth factor receptor, Ins-Rα, and fibroblast growth factor receptors. The present work aimed at analyzing the SOCS1 cell signaling and expression of proteins relevant to tumor development. An RNA microarray analysis of B16F10-Nex2 melanoma cells with SOCS1 silenced by shRNAi-SOCS1 was undertaken in comparison with cells transduced with the empty vector. Among 609 differentially expressed genes, c-Kit, Met and EphA3 cytokine/tyrosine-kinase (TK) receptors were down regulated. A significant decrease in the expression of TK receptors, the phosphorylation of mediators of ERK1/2 and p38 pathways and STAT3 (S727) were observed. Subcutaneous immunization with shR-SOCS1-transduced viable tumor cells rendered protection against melanoma in a syngeneic model, with decreased expression of PD-L1 and of matrix metallo-proteinases (MMPs) and CD-10 in those cells. The present work shows the role of SOCS1 in murine melanoma development and the potential of SOCS1-silenced tumor cells in raising an effective anti-melanoma immune response.
authors.affiliation: Experimental Oncology Unit, Department of Microbiology, Immunology and Parasitology, University of São Paulo, São Paulo, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Berzaghi
authors.affiliation: Recepta Biopharma São Paulo, Brazil.
authors.forename: V S C
authors.initials: VS
authors.lastname: Maia
authors.affiliation: Laboratory of Cancer Immunobiology, University of São Paulo, São Paulo, Brazil.
authors.forename: F V
authors.initials: FV
authors.lastname: Pereira
authors.affiliation: Immunology Department, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: F M
authors.initials: FM
authors.lastname: Melo
authors.affiliation: Experimental Oncology Unit, Department of Microbiology, Immunology and Parasitology, University of São Paulo, São Paulo, Brazil.
authors.forename: M S
authors.initials: MS
authors.lastname: Guedes
authors.affiliation: Laboratory of Cancer Immunobiology, University of São Paulo, São Paulo, Brazil.
authors.forename: C S T
authors.initials: CS
authors.lastname: Origassa
authors.affiliation: Immunotherapy Platform, Department of Immunology, MD Anderson Cancer Center, Houston Texas, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Scutti
authors.affiliation: Interdepartmental Group of Health Economics (Grides), Federal University of São Paulo, SP, Brazil.
authors.forename: A L
authors.initials: AL
authors.lastname: Matsuo
authors.affiliation: Immunology Department, Biomedical Sciences Institute IV, University of São Paulo, São Paulo, Brazil.
authors.forename: N O S
authors.initials: NO
authors.lastname: Câmara
authors.affiliation: Laboratory of Cancer Immunobiology, University of São Paulo, São Paulo, Brazil.
authors.forename: E G
authors.initials: EG
authors.lastname: Rodrigues
authors.affiliation: Experimental Oncology Unit, Department of Microbiology, Immunology and Parasitology, University of São Paulo, São Paulo, Brazil.|Recepta Biopharma São Paulo, Brazil.
authors.forename: L R
authors.initials: LR
authors.lastname: Travassos
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000378:metabolism*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D007109:Immunity; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D058950:Melanoma-Specific Antigens / Q000378:metabolism; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D020011:Protective Agents / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000378:metabolism*; D050656:Transcription Factor AP-2 / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism; D059016:Tumor Microenvironment; D015854:Up-Regulation / Q000235:genetics
chemical_list: D060890:B7-H1 Antigen; D019485:Bone Morphogenetic Proteins; C498919:Cd274 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D058950:Melanoma-Specific Antigens; D016328:NF-kappa B; D020011:Protective Agents; D051785:Smad Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050656:Transcription Factor AP-2; D016212:Transforming Growth Factor beta; D020794:Receptor Protein-Tyrosine Kinases; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I