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Predominant Rab-GTPase amplicons contributing to oral squamous cell carcinoma progression to metastasis.
da Silva, Sabrina Daniela; Marchi, Fabio Albuquerque; Xu, Bin; Bijian, Krikor; Alobaid, Faisal; Mlynarek, Alex; Rogatto, Silvia Regina; Hier, Michael; Kowalski, Luiz Paulo; Alaoui-Jamali, Moulay A.
Affiliation
  • da Silva SD; Department of Otolaryngology Head and Neck Surgery, Sir Mortimer B. Davis-Jewish General Hospital, Canada.
  • Marchi FA; Segal Cancer Centre and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Departments of Medicine, Oncology, and Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Canada.
  • Xu B; Department of Head and Neck Surgery and Otorhinolaryngology, AC Camargo Cancer Center and National Institute of Science and Technology on Oncogenomics (INCITO), Brazil.
  • Bijian K; NeoGene Laboratory, Department of Urology, Faculty of Medicine, UNESP, and International Research Center (CIPE), AC Camargo Cancer Center, Brazil.
  • Alobaid F; Inter-Institutional Grad Program on Bioinformatics, University of São Paulo, Brazil.
  • Mlynarek A; Segal Cancer Centre and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Departments of Medicine, Oncology, and Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Canada.
  • Rogatto SR; Segal Cancer Centre and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Departments of Medicine, Oncology, and Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Canada.
  • Hier M; Department of Otolaryngology Head and Neck Surgery, Sir Mortimer B. Davis-Jewish General Hospital, Canada.
  • Kowalski LP; Department of Otolaryngology Head and Neck Surgery, Sir Mortimer B. Davis-Jewish General Hospital, Canada.
  • Alaoui-Jamali MA; NeoGene Laboratory, Department of Urology, Faculty of Medicine, UNESP, and International Research Center (CIPE), AC Camargo Cancer Center, Brazil.
Oncotarget ; 6(26): 21950-63, 2015 Sep 08.
Article in En | MEDLINE | ID: mdl-26110570
ABSTRACT
Metastatic 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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Mouth Neoplasms / Carcinoma, Squamous Cell / Rab GTP-Binding Proteins / Head and Neck Neoplasms Type of study: Prognostic_studies Limits: Aged / Female / Humans / Male / Middle aged Language: En Journal: Oncotarget Year: 2015 Document type: Article Affiliation country: Canada

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Mouth Neoplasms / Carcinoma, Squamous Cell / Rab GTP-Binding Proteins / Head and Neck Neoplasms Type of study: Prognostic_studies Limits: Aged / Female / Humans / Male / Middle aged Language: En Journal: Oncotarget Year: 2015 Document type: Article Affiliation country: Canada