Predominant Rab-GTPase amplicons contributing to oral squamous cell carcinoma progression to metastasis

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorSilva, Sabrina Daniela da
dc.creatorMarchi, Fabio Albuquerque
dc.creatorXu, Bin
dc.creatorBijian, Krikor
dc.creatorAlobaid, Faisal
dc.creatorMlynarek, Alex
dc.creatorRogatto, Silvia Regina
dc.creatorHier, Michael
dc.creatorKowalski, Luiz Paulo
dc.creatorAlaoui-Jamali, Moulay A.
dc.date2015-12-07T15:37:39Z
dc.date2016-10-25T21:23:50Z
dc.date2015-12-07T15:37:39Z
dc.date2016-10-25T21:23:50Z
dc.date2015-09-08
dc.date.accessioned2017-04-06T09:31:36Z
dc.date.available2017-04-06T09:31:36Z
dc.identifierOncotarget, v. 6, n. 26, p. 21950-21963, 2015.
dc.identifier1949-2553
dc.identifierhttp://hdl.handle.net/11449/131562
dc.identifierhttp://acervodigital.unesp.br/handle/11449/131562
dc.identifier10.18632/oncotarget.4277
dc.identifierPM26110570.pdf
dc.identifier26110570
dc.identifierhttp://dx.doi.org/10.18632/oncotarget.4277
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/942102
dc.descriptionMetastatic oral squamous cell carcinoma (OSCC) is frequently associated with recurrent gene abnormalities at specific chromosomal loci. Here, we utilized array comparative genomic hybridization and genome-wide screening of metastatic and non-metastatic tongue tumors to investigate genes potentially contributing to OSCC progression to metastasis. We identified predominant amplifications of chromosomal regions that encompass the RAB5, RAB7 and RAB11 genes (3p24-p22, 3q21.3 and 8p11-12, respectively) in metastatic OSCC. The expression of these Rab GTPases was confirmed by immunohistochemistry in OSCC tissues from a cohort of patients with a follow-up of 10 years. A significant overexpression of Rab5, Rab7 and Rab11 was observed in advanced OSCC cases and co-overexpression of these Rabs was predictive of poor survival (log-rank test, P = 0.006). We generated a Rab interaction network and identified central Rab interactions of relevance to metastasis signaling, including focal adhesion proteins. In preclinical models, mRNA and protein expression levels of these Rab members were elevated in a panel of invasive OSCC cell lines, and their down-regulation prevented cell invasion at least in part via inhibition of focal adhesion disassembly. In summary, our results provide insights into the cooperative role of Rab gene amplifications in OSCC progression and support their potential utility as prognostic markers and therapeutic approach for advanced OSCC.
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.languageeng
dc.publisherOncotarget
dc.relationOncotarget
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectAcgh
dc.subjectGenomic
dc.subjectMetastasis
dc.subjectOral squamous cell carcinoma
dc.subjectRab gtpases
dc.titlePredominant Rab-GTPase amplicons contributing to oral squamous cell carcinoma progression to metastasis
dc.typeOtro


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