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

27 Citations (Scopus)

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

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Interleukin-13
Phosphatidylinositol 3-Kinases
Colonic Neoplasms
Neoplasm Metastasis
Proteins
TNF-Related Apoptosis-Inducing Ligand Receptors
Kinesin
src-Family Kinases
Liver
Liver Neoplasms
G-Protein-Coupled Receptors
Nude Mice
Microtubules
Cell Movement
Cell Survival
Phosphorylation
Cell Line
Antibodies

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Bartolomé, Rubén A. ; García-Palmero, Irene ; Torres, Sofía ; López-Lucendo, María ; Balyasnikova, Irina V. ; Casal, J. Ignacio. / IL13 receptor α2 signaling requires a scaffold protein, FAM120A, to activate the FAK and PI3K pathways in colon cancer metastasis. In: Cancer Research. 2015 ; Vol. 75, No. 12. pp. 2434-2444.
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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.",
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IL13 receptor α2 signaling requires a scaffold protein, FAM120A, to activate the FAK and PI3K pathways in colon cancer metastasis. / Bartolomé, Rubén A.; García-Palmero, Irene; Torres, Sofía; López-Lucendo, María; Balyasnikova, Irina V.; Casal, J. Ignacio.

In: Cancer Research, Vol. 75, No. 12, 15.06.2015, p. 2434-2444.

Research output: Contribution to journalArticle

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AU - Bartolomé, Rubén A.

AU - García-Palmero, Irene

AU - Torres, Sofía

AU - López-Lucendo, María

AU - Balyasnikova, Irina V.

AU - Casal, J. Ignacio

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N2 - 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.

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