Transforming growth factor-β1-induced epithelial-mesenchymal transition in human esophageal squamous cell carcinoma via the PTEN/PI3K signaling pathway

Zhang,Hong-Yan; Wang,Zhi-Qiang; Li,Yun-Yun; Wang,Feng; Zeng,Qing-Ru; Gao,Yuan; Xuan,Xiao-Yan; Li,Shan-Shan

doi:10.3892/or.2014.3453

Transforming growth factor-β1-induced epithelial-mesenchymal transition in human esophageal squamous cell carcinoma via the PTEN/PI3K signaling pathway

Authors:
- Hong-Yan Zhang
- Zhi-Qiang Wang
- Yun-Yun Li
- Feng Wang
- Qing-Ru Zeng
- Yuan Gao
- Xiao-Yan Xuan
- Shan-Shan Li
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Affiliations: Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Supersonics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Microbiology and Immunology, Basic Medical College of Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
Published online on: August 29, 2014 https://doi.org/10.3892/or.2014.3453
Pages: 2134-2142

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Abstract

Epithelial-mesenchymal transition (EMT) is a crucial step for the invasive and metastatic properties of malignant tumor cells during tumor progression. Numerous signaling pathways are involved in the process of EMT in cancer, such as the EMT-inducing signal transforming growth factor (TGF)-β and the recently demonstrated PTEN/PI3K signaling pathway. To date, no data have been reported concerning the influence of PTEN/PI3K signaling pathway on EMT in human esophageal squamous cell carcinoma (ESCC) and how TGF-β1 and PTEN/PI3K act through multiple interconnected signaling pathways to trigger events associated with EMT and tumor progression. Our data showed that the PTEN/PI3K pathway was active in human ESCC tissues in vivo, particularly in ESCC with decreased E-cadherin and increased vimentin protein expression, poor differentiation, deep invasion and lymph node metastasis, which are responsible for EMT and tumor progression. In addition, in the human ESCC cell line (EC-1) in vitro, TGF-β1 treatment markedly induced EMT, including morphological alterations, a decrease of E-cadherin and an increase of vimentin levels and enhanced mobility and invasiveness. Furthermore, the PTEN/PI3K pathway was also activated in the process of TGF-β1-induced EMT in EC-1 cells in vitro, whereas inhibition of the PTEN/PI3K pathway by using pcDNA3.1 PTEN partially blocked TGF-β1-induced EMT and reduced mobility and invasiveness. These studies suggest that TGF-β1 and the PTEN/PI3K signaling pathway contribute to EMT and the PTEN/PI3K signaling pathway is a key regulator of TGF-β1‑induced EMT in ESCC. Disruption of the PTEN/PI3K pathway involved in TGF-β1-induced EMT may provide possible routes for therapeutic intervention to ESCC.

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