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

Sabrina Daniela da Silva, Moulay A Alaoui-Jamali, Fernando Augusto Soares, Dirce Maria Carraro, Helena Paula Brentani, Michael Hier, Silvia Regina Rogatto, Luiz Paulo Kowalski

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstrakt

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.

OriginalsprogEngelsk
TidsskriftCancer
Vol/bind120
Udgave nummer3
Sider (fra-til)352-62
Antal sider11
ISSN0008-543X
DOI
StatusUdgivet - 1. feb. 2014
Udgivet eksterntJa

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