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Title

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

Other TitlesIL13Rα2 signaling in colorectal cancer metastasis
AuthorsBartolomé, Rubén Álvaro ; García-Palmero, Irene ; Torres, Sofía ; López-Lucendo, María F. ; Balyasnikova, Irina V.; Casal, J. Ignacio
KeywordsIL13Rα2
IL-13
FAM120A
PI3K
Src
Colon cancer metastasis
Issue Date15-Jun-2015
PublisherAmerican Association for Cancer Research
CitationCancer Res. 75; 2434 (2015)
AbstractIL-13 signaling through IL13Rα2 plays a critical role in colon cancer invasion and liver metastasis. Here, we studied the mechanism of signaling activation upon binding of IL-13 to IL13Rα2. IL13Rα2 immunoprecipitation followed by mass spectrometry analysis identified a scaffold protein, FAM120A (also known as c9orf10), as a signaling partner. We observed an overexpression of FAM120A in colon cancer cell lines and 55% of colon cancer samples. Co-immunoprecipitation experiments confirmed the interaction IL13Rα2-FAM120A. Furthermore, immunoprecipitation of FAM120A revealed its association with different protein networks and cell signaling pathways that can regulate the activity of IL13Rα2, including FAK, SRC, PI3K, G protein coupled receptors and TRAIL receptors. In addition, FAM120A was associated to 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. FAM120A recruits PI3K and works as a scaffold protein for PI3K and the Src family kinases (SFKs), enabling phosphorylation and activation of PI3K by SFKs. Silencing of FAM120A abolished IL-13-induced cell migration, invasion and survival. Finally, either blocking of IL13Rα2 with antibodies or silencing of FAM120A precluded liver colonization in nude mice and cancer metastasis. In conclusion, FAM120A constitutes a key protein in the IL-13/IL13Rα2 signaling activation pathway, which leads to cell invasion and liver metastasis in colon cancer and, probably, other diseases.
Description32 p.-7 fig.
Publisher version (URL)http://dx.doi.org/ 10.1158/0008-5472.CAN-14-3650
URIhttp://hdl.handle.net/10261/123035
DOI10.1158/0008-5472.CAN-14-3650
ISSN0008-5472
E-ISSN1538-7445
Appears in Collections:(CIB) Artículos
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