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Crosstalk between pro-survival sphingolipid metabolism and complement signaling induces inflammasome-mediated tumor metastasis.
Janneh, Alhaji H; Kassir, Mohamed Faisal; Atilgan, F Cansu; Lee, Han Gyul; Sheridan, Megan; Oleinik, Natalia; Szulc, Zdzislaw; Voelkel-Johnson, Christina; Nguyen, Hung; Li, Hong; Peterson, Yuri K; Marangoni, Elisabetta; Saatci, Ozge; Sahin, Ozgur; Lilly, Michael; Atkinson, Carl; Tomlinson, Stephen; Mehrotra, Shikhar; Ogretmen, Besim.
Afiliação
  • Janneh AH; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
  • Kassir MF; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
  • Atilgan FC; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
  • Lee HG; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
  • Sheridan M; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
  • Oleinik N; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
  • Szulc Z; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
  • Voelkel-Johnson C; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Department of Microbiology and Immunology, M
  • Nguyen H; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Department of Microbiology and Immunology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
  • Li H; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Department of Public Health, College of Medicine, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
  • Peterson YK; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
  • Marangoni E; Translational Research Department, Institut Curie, Paris, France.
  • Saatci O; Department of Drug Discovery and Biomedical Sciences, School of Pharmacy, University of South Carolina, Columbia, SC 29208, USA.
  • Sahin O; Department of Drug Discovery and Biomedical Sciences, School of Pharmacy, University of South Carolina, Columbia, SC 29208, USA.
  • Lilly M; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
  • Atkinson C; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Department of Microbiology and Immunology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
  • Tomlinson S; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Department of Microbiology and Immunology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
  • Mehrotra S; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Department of Microbiology and Immunology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
  • Ogretmen B; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA. Electronic address: ogretmen@musc.edu.
Cell Rep ; 41(10): 111742, 2022 12 06.
Article em En | MEDLINE | ID: mdl-36476873
ABSTRACT
Crosstalk between metabolic and signaling events that induce tumor metastasis remains elusive. Here, we determine how oncogenic sphingosine 1-phosphate (S1P) metabolism induces intracellular C3 complement activation to enhance migration/metastasis. We demonstrate that increased S1P metabolism activates C3 complement processing through S1P receptor 1 (S1PR1). S1P/S1PR1-activated intracellular C3b-α'2 is associated with PPIL1 through glutamic acid 156 (E156) and aspartic acid 111 (D111) residues, resulting in NLRP3/inflammasome induction. Inactivation mutations of S1PR1 to prevent S1P signaling or mutations of C3b-α'2 to prevent its association with PPIL1 attenuate inflammasome activation and reduce lung colonization/metastasis in mice. Also, activation of the S1PR1/C3/PPIL1/NLRP3 axis is highly associated with human metastatic melanoma tissues and patient-derived xenografts. Moreover, targeting S1PR1/C3/PPIL1/NLRP3 signaling using molecular, genetic, and pharmacologic tools prevents lung colonization/metastasis of various murine cancer cell lines using WT and C3a-receptor1 knockout (C3aR1-/-) mice. These data provide strategies for treating high-grade/metastatic tumors by targeting the S1PR1/C3/inflammasome axis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Inflamassomos / Melanoma Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Inflamassomos / Melanoma Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos