Interferon-induced transmembrane proteins IFITM1 and IFITM3 (IFITM1/3) play a role in both RNA viral restriction and in human cancer progression. Using immunohistochemical staining of FFPE tissue, we identified subgroups of cervical cancer patients where IFITM1/3 protein expression is inversely related to metastasis. Guide RNA-CAS9 methods were used to develop an isogenic IFITM1/IFITM3 double null cervical cancer model in order to define dominant pathways triggered by presence or absence of IFITM1/3 signalling. A pulse SILAC methodology identified IRF1, HLA-B, and ISG15 as the most dominating IFNγ inducible proteins whose synthesis was attenuated in the IFITM1/IFITM3 double-null cells. Conversely, SWATH-IP mass spectrometry of ectopically expressed SBP-tagged IFITM1 identified ISG15 and HLA-B as dominant co-associated proteins. ISG15ylation was attenuated in IFNγ treated IFITM1/IFITM3 double-null cells. Proximity ligation assays indicated that HLA-B can interact with IFITM1/3 proteins in parental SiHa cells. Cell surface expression of HLA-B was attenuated in IFNγ treated IFITM1/IFITM3 double-null cells. SWATH-MS proteomic screens in cells treated with IFITM1-targeted siRNA cells resulted in the attenuation of an interferon regulated protein subpopulation including MHC Class I molecules as well as IFITM3, STAT1, B2M, and ISG15. These data have implications for the function of IFITM1/3 in mediating IFNγ stimulated protein synthesis including ISG15ylation and MHC Class I production in cancer cells. The data together suggest that pro-metastatic growth associated with IFITM1/3 negative cervical cancers relates to attenuated expression of MHC Class I molecules that would support tumor immune escape.

• Klíčová slova
• CAS9 gene editing, Cervical cancer, IFITM1, Interferon, MHC Class I molecule, SILAC mass spectrometry,
• MeSH
• buněčné linie MeSH
• diferenciační antigeny fyziologie   MeSH
• histokompatibilita - antigeny třídy I metabolismus   MeSH
• lidé MeSH
• membránové proteiny fyziologie   MeSH
• nádory děložního čípku metabolismus   MeSH
• proteiny vázající RNA fyziologie   MeSH
• proteosyntéza fyziologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• diferenciační antigeny MeSH
• histokompatibilita - antigeny třídy I MeSH
• IFITM3 protein, human MeSH Prohlížeč
• leu-13 antigen MeSH Prohlížeč
• membránové proteiny MeSH
• proteiny vázající RNA MeSH

CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) is a transmembrane glycoprotein belonging to the carcinoembryonic antigen (CEA) family and immunoglobulin superfamily. It is localized mainly in the apical domains of polarized epithelia, leukocytes and endothelia. With respect to this wide tissue distribution the research is focused on the study of its biological functions. Structural and functional analyses show that the extracellular domain of CEACAM1 participates in homotypic and heterotypic adhesion, whereas the cytoplasmic domain takes part in cell growth inhibition and signal transduction. Whereas CEA is highly expressed in adenocarcinomas, CEACAM1 expression is down regulated in many tumors and its tumor-supressive function was confirmed. CEACAM1 also takes part in insulin metabolism, acts as a promotor of cholesterol crystallization and serves as a binding receptor for certain bacterial strains in humans as well as hepatitis virus in mice.

• MeSH
• buněčná adheze fyziologie   MeSH
• CD antigeny chemie   fyziologie   MeSH
• diferenciační antigeny chemie   fyziologie   MeSH
• inzulin fyziologie   MeSH
• karcinoembryonální antigen chemie   fyziologie   MeSH
• lidé MeSH
• molekuly buněčné adheze chemie   fyziologie   MeSH
• nádory patofyziologie   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• CD antigeny MeSH
• CD66 antigens MeSH Prohlížeč
• diferenciační antigeny MeSH
• inzulin MeSH
• karcinoembryonální antigen MeSH
• molekuly buněčné adheze MeSH