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

Autor:	Rodrigues PC; Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, SP, Brazil.; Unit of Cancer Research and Translational Medicine, Faculty of Medicine and Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland., Sawazaki-Calone I; Oral Pathology and Oral Medicine, Dentistry School, Western Paraná State University, Cascavel, PR, Brazil., Ervolino de Oliveira C; Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, SP, Brazil., Soares Macedo CC; Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, SP, Brazil., Dourado MR; Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, SP, Brazil.; Unit of Cancer Research and Translational Medicine, Faculty of Medicine and Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland., Cervigne NK; Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, SP, Brazil.; Current/Present address: Clinical Department, Faculty of Medicine of Jundiai, Jundiai, SP, Brazil., Miguel MC; Department of Dentistry, Federal University of Rio Grande do Norte, Natal, RN, Brazil., Ferreira do Carmo A; Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, SP, Brazil.; Department of Dentistry, Federal University of Rio Grande do Norte, Natal, RN, Brazil., Lambert DW; Integrated Biosciences, School of Clinical Dentistry and Sheffield Cancer Centre, University of Sheffield, Sheffield, United Kingdom., Graner E; Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, SP, Brazil., Daniela da Silva S; Departments 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.; Otolaryngology-Head and Neck Surgery, Faculty of Medicine, McGill University, Montreal, Quebec, Canada., Alaoui-Jamali MA; Departments 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.; Otolaryngology-Head and Neck Surgery, Faculty of Medicine, McGill University, Montreal, Quebec, Canada., Paes Leme AF; Brazilian Biosciences National Laboratory-CNPEM, Campinas, SP, Brazil., Salo TA; Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, SP, Brazil.; Unit of Cancer Research and Translational Medicine, Faculty of Medicine and Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland.; Institute of Oral and Maxillofacial Disease, University of Helsinki, and HUSLAB, Department of Pathology, Helsinki University Hospital, Helsinki, Finland., Coletta RD; Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, SP, Brazil.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2017 Aug 19; Vol. 8 (43), pp. 74736-74754. Date of Electronic Publication: 2017 Aug 19 (Print Publication: 2017).
DOI:	10.18632/oncotarget.20360
Abstrakt:	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. Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no competing interests.
Databáze:	MEDLINE
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