TWIST1 is a molecular marker for a poor prognosis in oral cancer and represents a potential therapeutic target

Authors

  • Sabrina Daniela da Silva PhD,

    Corresponding author
    1. Department of Head and Neck Surgery and Otorhinolaryngology, AC Camargo Cancer Center, São Paulo, Brazil
    2. Lady Davis Institute for Medical Research and Segal Cancer Center, Jewish General Hospital, Montreal, Quebec, Canada
    3. Department of Otolaryngology-Head and Neck Surgery, McGill University, Montreal, Quebec, Canada
    • Corresponding authors: Sabrina Daniela da Silva, PhD, and Moulay A. Alaoui-Jamali, PhD, Departments of Medicine and Oncology, Otolaryngology-Head and Neck Surgery, McGill University, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Cote St. Catherine Road, Montreal, QC, H3T 1E2, Canada; Fax: (514) 340-7576; sabrinadaniela@hotmail.com; moulay.alaoui-jamali@mcgill.ca

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  • Moulay A. Alaoui-Jamali PhD,

    1. Lady Davis Institute for Medical Research and Segal Cancer Center, Jewish General Hospital, Montreal, Quebec, Canada
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  • Fernando Augusto Soares MD, PhD,

    1. Department of Anatomic Pathology, AC Camargo Cancer Center and Faculty of Dentistry, University of São Paulo, São Paulo, Brazil
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  • Dirce Maria Carraro PhD,

    1. Laboratory of Molecular Biology, AC Camargo Cancer Center, São Paulo, Brazil
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  • Helena Paula Brentani MD, PhD,

    1. Laboratory of Biotechnology, AC Camargo Cancer Center, São Paulo, Brazil
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  • Michael Hier MD,

    1. Department of Otolaryngology-Head and Neck Surgery, McGill University, Montreal, Quebec, Canada
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  • Silvia Regina Rogatto PhD,

    1. NeoGene Laboratory, Department of Urology, São Paulo State University and AC Camargo Cancer Center, São Paulo, Brazil
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  • Luiz Paulo Kowalski MD, PhD

    1. Department of Head and Neck Surgery and Otorhinolaryngology, AC Camargo Cancer Center, São Paulo, Brazil
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Abstract

BACKGROUND

Locoregional recurrence and distant metastases are ominous events in patients with advanced oral squamous cell carcinoma (OSCC). The objective of this study was to identify functional biomarkers that are predictive of OSCC progression to metastasis.

METHODS

The expression profile of a network of epithelial-mesenchymal transition (EMT) genes was investigated in a large cohort of patients with progressive OSCC using a complimentary DNA microarray platform coupled to quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical analyses. Therapeutic potential was investigated in vitro and in vivo using an orthotopic mouse model of metastatic OSCC growing in the tongue microenvironment.

RESULTS

Among deregulated EMT genes, the Twist-related protein 1 (TWIST1) transcription factor and several of its regulated genes were significantly overexpressed across advanced stages of OSCC. This result was corroborated by the clinical observation that Twist1 up-regulation predicted the occurrence of lymph node and lung metastases as well as poor patient survival. In support of Twist1 as a driver of OSCC progression, the up-regulation of Twist1 was observed in cells isolated from patients with metastatic OSCC. The inhibition of Twist1 in these metastatic cells induced a potent inhibition of cell invasiveness in vitro as well as progression in vivo.

CONCLUSIONS

The current results provide evidence for the prognostic value and therapeutic potential of a network of Twist genes in patients with advanced OSCC. Cancer 2014;120:352–362. © 2013 American Cancer Society.

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