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

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dc.contributor.author Rodrigues, Priscila Campioni
dc.contributor.author Sawazaki-Calone, Iris
dc.contributor.author de Oliveira, Carine Ervolino
dc.contributor.author Soares Macedo, Carolina Carneiro
dc.contributor.author Dourado, Mauricio Rocha
dc.contributor.author Cervigne, Nilva K.
dc.contributor.author Miguel, Marcia Costa
dc.contributor.author do Carmo, Andreia Ferreira
dc.contributor.author Lambert, Daniel W.
dc.contributor.author Graner, Edgard
dc.contributor.author da Silva, Sabrina Daniela
dc.contributor.author Alaoui-Jamali, Moulay A.
dc.contributor.author Paes Leme, Adriana Franco
dc.contributor.author Salo, Tuula A.
dc.contributor.author Coletta, Ricardo D.
dc.date.accessioned 2017-10-13T07:11:01Z
dc.date.available 2017-10-13T07:11:01Z
dc.date.issued 2017-09-26
dc.identifier.citation 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
dc.identifier.other PURE: 90981502
dc.identifier.other PURE UUID: 3cd2ab2c-08ed-4781-8b0a-fb6cf9d48ab3
dc.identifier.other WOS: 000411760400112
dc.identifier.other Scopus: 85030106202
dc.identifier.other ORCID: /0000-0001-6039-0088/work/51804603
dc.identifier.uri http://hdl.handle.net/10138/225782
dc.description.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. en
dc.format.extent 19
dc.language.iso eng
dc.relation.ispartof Oncotarget
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject fascin
dc.subject plectin
dc.subject oral squamous cell carcinoma
dc.subject migration e invasion
dc.subject prognosis
dc.subject EPITHELIAL-MESENCHYMAL TRANSITION
dc.subject CANCER-CELLS
dc.subject DOWN-REGULATION
dc.subject UP-REGULATION
dc.subject LUNG-CANCER
dc.subject MIR-138
dc.subject EXPRESSION
dc.subject PROLIFERATION
dc.subject METASTASIS
dc.subject FIBROBLASTS
dc.subject 3122 Cancers
dc.subject 3111 Biomedicine
dc.title Fascin promotes migration and invasion and is a prognostic marker for oral squamous cell carcinoma en
dc.type Article
dc.contributor.organization HUSLAB
dc.contributor.organization Department of Oral and Maxillofacial Diseases
dc.contributor.organization Clinicum
dc.contributor.organization University of Helsinki
dc.contributor.organization Medicum
dc.contributor.organization Department of Pathology
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.18632/oncotarget.20360
dc.relation.issn 1949-2553
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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