IL13 receptor α2 signaling requires a scaffold protein, FAM120A, to activate the FAK and PI3K pathways in colon cancer metastasis

Rubén A. Bartolomé, Irene García-Palmero, Sofía Torres, María López-Lucendo, Irina V. Balyasnikova, J. Ignacio Casal*

*Corresponding author for this work

Research output: Contribution to journalArticle

32 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2434-2444
Number of pages11
JournalCancer Research
Volume75
Issue number12
DOIs
StatePublished - Jun 15 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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