Fascin promotes migration and invasion and is a prognostic marker for oral squamous cell carcinoma

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Rodrigues , P C , Sawazaki-Calone , I , de Oliveira , C E , Soares Macedo , C C , Dourado , M R , Cervigne , N K , Miguel , M C , do Carmo , A F , Lambert , D W , Graner , E , da Silva , S D , Alaoui-Jamali , M A , Paes Leme , A F , Salo , T A & Coletta , R D 2017 , ' Fascin promotes migration and invasion and is a prognostic marker for oral squamous cell carcinoma ' , Oncotarget , vol. 8 , no. 43 , pp. 74736-74754 . https://doi.org/10.18632/oncotarget.20360

Title: Fascin promotes migration and invasion and is a prognostic marker for oral squamous cell carcinoma
Author: Rodrigues, Priscila Campioni; Sawazaki-Calone, Iris; de Oliveira, Carine Ervolino; Soares Macedo, Carolina Carneiro; Dourado, Mauricio Rocha; Cervigne, Nilva K.; Miguel, Marcia Costa; do Carmo, Andreia Ferreira; Lambert, Daniel W.; Graner, Edgard; da Silva, Sabrina Daniela; Alaoui-Jamali, Moulay A.; Paes Leme, Adriana Franco; Salo, Tuula A.; Coletta, Ricardo D.
Other contributor: University of Helsinki, HUSLAB





Date: 2017-09-26
Language: eng
Number of pages: 19
Belongs to series: Oncotarget
ISSN: 1949-2553
DOI: https://doi.org/10.18632/oncotarget.20360
URI: http://hdl.handle.net/10138/225782
Abstract: 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.
Subject: fascin
plectin
oral squamous cell carcinoma
migration e invasion
prognosis
EPITHELIAL-MESENCHYMAL TRANSITION
CANCER-CELLS
DOWN-REGULATION
UP-REGULATION
LUNG-CANCER
MIR-138
EXPRESSION
PROLIFERATION
METASTASIS
FIBROBLASTS
3122 Cancers
3111 Biomedicine
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