The EMT transcription factor, Twist1, as a novel therapeutic target for pulmonary sarcomatoid carcinomas

Abstract

Pulmonary sarcomatoid carcinomas (PSCs) are a rare subtype of non-small-cell lung cancer and are typically biphasic neoplasms. No effective treatment for PSCs is currently available in clinical practice. The expression of the epithelial-mesenchymal transition (EMT) transcription factors, Twist1, Slug and Snail, as well as the EMT phenotype and vasculogenic mimicry (VM) were analysed in 41 PSC and 79 pulmonary squamous carcinoma (PSCC) samples. Compared with the PSCCs, the PSCs exhibited an EMT phenotype and VM, and they also exhibited an increased expression of the Twist1, Slug, Snail and VM markers. Twist1 expression was associated with metastasis and TNM stage. Twist1-positive patients exhibited a poorer prognosis for overall survival (OS) than those with Twist1-negative PSCs. Transforming growth factor p1 (TGFβ1) was used to induce an EMT transition in a PSCC cell line. SK-MES-1 cells treated with TGFβ1 exhibited an increased expression of Twist1. The EMT phenotype, VM and increased migratory and invasive abilities were induced following TGFβ1 treatment. Importantly, in cells treated with TGFβ1, the EMT phenotype was reversed, VM marker expression was decreased, and the migratory and invasive ability of the PSCC cell line was decreased following Twist1 knockdown. Collectively, this study provides a new perspective of Twist1 in the aggressiveness of PSCs. The identification of Twist1 as an independent marker of poor prognoses may lead to the development of novel strategies for improving the treatment of patients with PSC.