Fascin promotes migration and invasion and is a prognostic marker for oral squamous cell carcinoma
Campioni Rodrigues, Priscila; Sawazaki-Calone, Iris; Ervolino de Oliveira, Carine; Carneiro Soares Macedo, Carolina; Rocha Dourado, Mauricio; Cervigne, Nilva K.; Costa Miguel, Marcia; Ferreira do Carmo, Andreia; Lambert, Daniel W.; Graner, Edgard; da Silva, Sabrina Daniela; Alaoui-Jamali, Moulay A.; Paes Leme, Adriana Franco; Salo, Tuula A.; Coletta, Ricardo D. (2017-08-19)
Campioni Rodrigues, P., Sawazaki-Calone, I., Ervolino de Oliveira, C., Carneiro Soares Macedo, C., Rocha Dourado, M., Cervigne, N., Costa Miguel, M., Ferreira do Carmo, A., Lambert, D., Graner, E., Daniela da Silva, S., Alaoui-Jamali, M., Franco Paes Leme, A., Salo, T., Coletta, R. (2017) Fascin promotes migration and invasion and is a prognostic marker for oral squamous cell carcinoma. Oncotarget, 8(43): 74736-74754. doi:10.18632/oncotarget.20360
Rodrigues et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Oral squamous cell carcinoma (OSCC) prognosis is related to clinical stage and histological grade. However, this stratification needs to be refined. We conducted a comparative proteome study in microdissected samples from normal oral mucosa and OSCC to identify biomarkers for malignancy. Fascin and plectin were identified as differently expressed and both are implicated in several malignancies, but the clinical impacts of aberrant fascin and plectin expression in OSCCs remains largely unknown. Immunohistochemistry and real-time quantitative PCR were carried out in ex vivo OSCC samples and cell lines. A loss-of-function strategy using shRNA targeting fascin was employed to investigate in vitro and in vivo the fascin role on oral tumorigenesis. Transfections of microRNA mimics were performed to determine whether the fascin overexpression is regulated by miR-138 and miR-145. We found that fascin and plectin are frequently upregulated in OSCC samples and cell lines, but only fascin overexpression is an independent unfavorable prognostic indicator of disease-specific survival. In combination with advanced T stage, high fascin level is also an independent factor of disease-free survival. Knockdown of fascin in OSCC cells promoted cell adhesion and inhibited migration, invasion and EMT, and forced expression of miR-138 in OSCC cells significantly decreased the expression of fascin. In addition, fascin downregulation leads to reduced filopodia formation and decrease on paxillin expression. The subcutaneous xenograft model showed that tumors formed in the presence of low levels of fascin were significantly smaller compared to those formed with high fascin levels. Collectively, our findings suggest that fascin expression correlates with disease progression and may serve as a prognostic marker and therapeutic target for patients with OSCC.
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