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

Liu,Tieju; Zhao,Xiulan; Zheng,Xu; Zheng,Yanjun; Dong,Xueyi; Zhao,Nan; Liao,Shihan; Sun,Baocun

doi:10.3892/ijo.2020.4972

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

Authors:
- Tieju Liu
- Xiulan Zhao
- Xu Zheng
- Yanjun Zheng
- Xueyi Dong
- Nan Zhao
- Shihan Liao
- Baocun Sun
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Affiliations: Department of Pathology, Tianjin Medical University, Tianjin 300070, P.R. China
Published online on: January 29, 2020 https://doi.org/10.3892/ijo.2020.4972
Pages: 750-760
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 β1 (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.

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