Agrin has a pathological role in the progression of oral cancer

César Rivera, Flávia Silva Zandonadi, Celeste Sánchez-Romero, Ciro Dantas Soares, Daniela Campos Granato, Wilfredo Alejandro González-Arriagada, Adriana Franco Paes Leme*

*Autor correspondiente de este trabajo

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

18 Citas (Scopus)

Resumen

Background: The extracellular matrix modulates the hallmarks of cancer. Here we examined the role of agrin - a member of this matrix - in progression of oral squamous cell carcinoma (OSCC). Methods: We evaluated the immunohistochemical expression of agrin in OSCC and dysplasias. Benign lesions were used as control. In subsequent experiments, we investigated whether the silencing of agrin interferes with tumour expansion both in vitro as well as in vivo. To gain insights into the role of agrin, we identified its protein network (interactome) using mass spectrometry-based proteomics and bioinformatics. Finally, we evaluated the clinical relevance of agrin interactome. Results: Agrin was elevated in malignant and premalignant lesions. Further, we show that agrin silencing interferes with cancer cell motility, proliferation, invasion, colony and tumour spheroid formation, and it also reduces the phosphorylation of FAK, ERK and cyclin D1 proteins in OSCC cells. In orthotopic model, agrin silencing reduces tumour aggressiveness, like vascular and neural invasion. From a clinical perspective, agrin contextual hubs predict a poor clinical prognosis related with overall survival. Conclusions: Altogether, our results demonstrate that agrin is a histological marker for the progression of oral cancer and is a strong therapeutic target candidate for both premalignant and OSCC lesions.

Idioma originalInglés
Páginas (desde-hasta)1628-1638
Número de páginas11
PublicaciónBritish Journal of Cancer
Volumen118
N.º12
DOI
EstadoPublicada - 1 jun 2018

Nota bibliográfica

Funding Information:
CONICYT Becas-Chile Scholarship 8540/2014 (to C.R.), FONDECYT 11140507 (to W.A. G.-A.) and FAPESP Grants 2009/54067-3, 2010/19278-0 and 2016/07846-0 (to A.F.P.L.) supported this work.

Funding Information:
Funding: CONICYT Becas-Chile Scholarship 8540/2014 (to C.R.), FONDECYT 11140507 (to W.A. G.-A.) and FAPESP Grants 2009/54067-3, 2010/19278-0 and 2016/07846-0 (to A.F.P.L.) supported this work.

Publisher Copyright:
© 2018 Cancer Research UK.

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