TWIST1 regulates proliferation, migration, and invasion and is a prognostic marker for oral tongue squamous cell carcinoma

• Published in: Journal of oral pathology & medicine Vol. 52; no. 2; pp. 127 - 135
• Main Authors: Morais, Everton Freitas, Farias Morais, Hannah Gil, Moura Santos, Edilmar, Barboza, Carlos Augusto Galvão, Téo, Fábio Haach, Salo, Tuula, Coletta, Ricardo D., Almeida Freitas, Roseana
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01-02-2023
• Subjects: Apoptosis; biological behavior; Cadherins - metabolism; Cancer; Carcinogenesis; Carcinoma, Squamous Cell - pathology; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cytoplasm; Dysplasia; Epithelial-Mesenchymal Transition - physiology; epithelial–mesenchymal transition; Expression vectors; Head and Neck Neoplasms; Humans; Mesenchyme; Metastases; Nuclear Proteins; oral carcinogenesis; Oral carcinoma; Prognosis; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; Therapeutic applications; Therapeutic targets; Tongue; Tongue Neoplasms - pathology; Transcription factors; Twist-Related Protein 1 - metabolism; epithelial-mesenchymal transition; oral carcinogenesis; prognosis; biological behavior
• ISSN: 0904-2512; 1600-0714
• DOI: 10.1111/jop.13377

Background
Epithelial–mesenchymal transition is one of the main mechanisms for tumor progression and metastasis. Transcription factors such as TWIST1 are key regulators of the epithelial–mesenchymal transition and are regarded as potential therapeutic targets for the treatment of cancer. The purpose of this study was to examine TWIST1 as a possible epithelial‐mesenchymal transition‐related prognostic biomarker in oral epithelial dysplasia and oral tongue squamous cell carcinomas, as well as the biological behavior of TWIST1‐silencing in oral tongue squamous cell carcinomas cell lines.
Methods
Immunohistochemical analysis of TWIST1, E‐cadherin, and N‐cadherin was carried out in 47 samples representing oral epithelial dysplasia and 41 oral tongue squamous cell carcinomas. The suppression of TWIST1 expression was performed using shRNA‐expression vectors in HSC‐3 and SCC‐9 cells to investigate in vitro the impact of TWIST1 on proliferation, apoptosis, viability, migration, and invasion of SCC‐9 and HSC‐3 cells.
Results
The expression of nuclear TWIST1 was significantly higher in oral tongue squamous cell carcinomas than in oral epithelial dysplasis (p < 0.0001), whereas TWIST1 in the cytoplasm was more expressed in oral epithelial dysplasis (p = 0.012). The high cytoplasmic expression of TWIST1 was significantly associated with shortened overall survival (p < 0.05), and increased nuclear TWIST1 expression was significantly related to high risk of recurrence (p = 0.03). Knockdown of TWIST1 in oral tongue squamous cell carcinomas cells induced the expression of E‐cadherin and inhibited N‐cadherin, which were followed by decreased proliferation, migration, and invasion.
Conclusions
Our research suggests that TWIST1 is linked to the development of oral tongue carcinogenesis and may be used as a prognostic indicator and therapeutic target for oral tongue squamous cell carcinomas patients.