2026-04-29T12:25:17Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/167502025-04-01T07:24:21Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19617
Repisalud
author
Bartolomé, Rubén A
author
Martín-Regalado, Ángela
author
Pintado-Berninches, Laura
author
Robles, Javier
author
Ramírez-González, María A
author
Boukich, Issam
author
Sánchez-Gómez, Pilar
author
Balyasnikova, Irina V
author
Casal, José Ignacio
funder
Ministerio de Universidades (España)
funder
Comunidad de Madrid (España)
funder
Unión Europea. Comisión Europea. NextGenerationEU
funder
Agencia Estatal de Investigación (España)
funder
Ministerio de Ciencia e Innovación (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
NIH - National Institute of Neurological Disorders and Stroke (NINDS) (Estados Unidos)
funder
Instituto de Salud Carlos III
2023-12-05T09:27:01Z
2023-12-05T09:27:01Z
2023-11-14
Cell Death Dis. 2023 Nov 14;14(11):742.
10.1038/s41419-023-06255-4
2041-4889
Cell death & disease
37963919
http://hdl.handle.net/20.500.12105/16750
Interleukin 13 receptor alpha 2 (IL13Rα2) is a relevant therapeutic target in glioblastoma (GBM) and other tumors associated with tumor growth and invasion. In a previous study, we demonstrated that protein tyrosine phosphatase 1B (PTP1B) is a key mediator of the IL-13/IL13Rα2 signaling pathway. PTP1B regulates cancer cell invasion through Src activation. However, PTP1B/Src downstream signaling mechanisms that modulate the invasion process remain unclear. In the present research, we have characterized the PTP1B interactome and the PTP1B-associated phosphoproteome after IL-13 treatment, in different cellular contexts, using proteomic strategies. PTP1B was associated with proteins involved in signal transduction, vesicle transport, and with multiple proteins from the NF-κB signaling pathway, including Tenascin-C (TNC). PTP1B participated with NF-κB in TNC-mediated proliferation and invasion. Analysis of the phosphorylation patterns obtained after PTP1B activation with IL-13 showed increased phosphorylation of the transcription factor Schnurri-3 (SHN3), a reported competitor of NF-κB. SHN3 silencing caused a potent inhibition in cell invasion and proliferation, associated with a down-regulation of the Wnt/β-catenin pathway, an extensive decline of MMP9 expression and the subsequent inhibition of tumor growth and metastasis in mouse models. Regarding clinical value, high expression of SHN3 was associated with poor survival in GBM, showing a significant correlation with the classical and mesenchymal subtypes. In CRC, SHN3 expression showed a preferential association with the mesenchymal subtypes CMS4 and CRIS-B. Moreover, SHN3 expression strongly correlated with IL13Rα2 and MMP9-associated poor prognosis in different cancers. In conclusion, we have uncovered the participation of SNH3 in the IL-13/IL13Rα2/PTP1B pathway to promote tumor growth and invasion. These findings support a potential therapeutic value for SHN3.
eng
Schnurri-3 drives tumor growth and invasion in cancer cells expressing interleukin-13 receptor alpha 2
research article
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