Schnurri-3 drives tumor growth and invasion in cancer cells expressing interleukin-13 receptor alpha 2.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
14 Nov 2023
14 Nov 2023
Historique:
received:
14
03
2023
accepted:
30
10
2023
revised:
23
10
2023
medline:
15
11
2023
pubmed:
15
11
2023
entrez:
14
11
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37963919
doi: 10.1038/s41419-023-06255-4
pii: 10.1038/s41419-023-06255-4
pmc: PMC10645886
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
742Subventions
Organisme : Comunidad de Madrid
ID : IND2019/BMD-17153
Organisme : Comunidad de Madrid
ID : IND2022/BMD-23554
Organisme : Comunidad de Madrid
ID : S2022/BMD-7212
Organisme : Comunidad de Madrid
ID : IND2022/BMD-23554
Organisme : Comunidad de Madrid
ID : IND2019/BMD-17153
Organisme : Ministerio de Educación, Cultura y Deporte (Ministry of Education, Culture and Sports, Spain)
ID : CA1/RSUE/2021-00208
Informations de copyright
© 2023. The Author(s).
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