title: IL13 Receptor α2 Signaling Requires a Scaffold Protein, FAM120A, to Activate the FAK and PI3K Pathways in Colon Cancer Metastasis.
abstract: IL13 signaling through its receptor IL13Rα2 plays a critical role in colon cancer invasion and liver metastasis, but the mechanistic features of this process are obscure. In this study, we identified a scaffold protein, FAM120A (C9ORF10), as a signaling partner in this process. FAM120A was overexpressed in human colon cancer cell lines and 55% of human colon cancer specimens. IL13Rα2-FAM120A coimmunoprecipitation experiments revealed further signaling network associations that could regulate the activity of IL13Rα2, including FAK, SRC, PI3K, G-protein-coupled receptors, and TRAIL receptors. In addition, FAM120A associated with kinesins and motor proteins involved in cargo movement along microtubules. IL13Rα2-triggered activation of the FAK and PI3K/AKT/mTOR pathways was mediated by FAM120A, which also recruited PI3K and functioned as a scaffold protein to enable phosphorylation and activation of PI3K by Src family kinases. FAM120A silencing abolished IL13-induced cell migration, invasion, and survival. Finally, antibody blockade of IL13Rα2 or FAM120A silencing precluded liver colonization in nude mice or metastasis. In conclusion, we identified FAM120A in the IL13/IL13Rα2 signaling pathway as a key mediator of invasion and liver metastasis in colon cancer.
authors.affiliation: Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain.
authors.forename: Rubén A
authors.initials: RA
authors.lastname: Bartolomé
authors.affiliation: Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: García-Palmero
authors.affiliation: Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain.
authors.forename: Sofía
authors.initials: S
authors.lastname: Torres
authors.affiliation: Proteomics Facility, Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: López-Lucendo
authors.affiliation: The Brain Tumor Center, University of Chicago, Chicago, Illinois.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Balyasnikova
authors.affiliation: Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain. icasal@cib.csic.es.
authors.forename: J Ignacio
authors.initials: JI
authors.lastname: Casal
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism; D053661:Interleukin-13 Receptor alpha1 Subunit; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D053660:Receptors, Interleukin-13 / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D019869:Phosphatidylinositol 3-Kinases; D016601:RNA-Binding Proteins; D053660:Receptors, Interleukin-13; C534604:FAM120A protein, human; C578095:IL13 protein, human; C508181:IL13RA1 protein, human