Fascin promotes migration and invasion and is a prognostic marker for oral squamous cell carcinoma
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Priscila Campioni Rodrigues1,2, Iris Sawazaki-Calone3, Carine Ervolino de Oliveira1, Carolina Carneiro Soares Macedo1, Mauricio Rocha Dourado1,2, Nilva K. Cervigne1,10, Marcia Costa Miguel4, Andreia Ferreira do Carmo1,4, Daniel W. Lambert5, Edgard Graner1, Sabrina Daniela da Silva6,7, Moulay A. Alaoui-Jamali6,7, Adriana Franco Paes Leme8, Tuula A. Salo1,2,9 and Ricardo D. Coletta1
1Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, SP, Brazil
2Unit of Cancer Research and Translational Medicine, Faculty of Medicine and Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
3Oral Pathology and Oral Medicine, Dentistry School, Western Paraná State University, Cascavel, PR, Brazil
4Department of Dentistry, Federal University of Rio Grande do Norte, Natal, RN, Brazil
5Integrated Biosciences, School of Clinical Dentistry and Sheffield Cancer Centre, University of Sheffield, Sheffield, United Kingdom
6Departments of Medicine, Oncology, Pharmacology and Therapeutics, Segal Cancer Centre and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada
7Otolaryngology-Head and Neck Surgery, Faculty of Medicine, McGill University, Montreal, Quebec, Canada
8Brazilian Biosciences National Laboratory-CNPEM, Campinas, SP, Brazil
9Institute of Oral and Maxillofacial Disease, University of Helsinki, and HUSLAB, Department of Pathology, Helsinki University Hospital, Helsinki, Finland
10Current/Present address: Clinical Department, Faculty of Medicine of Jundiai, Jundiai, SP, Brazil
Priscila Campioni Rodrigues, email: [email protected]
Keywords: fascin, plectin, oral squamous cell carcinoma, migration and invasion, prognosis
Received: April 07, 2017 Accepted: July 12, 2017 Published: August 19, 2017
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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