Ski prevents TGF-β-induced EMT and cell invasion by repressing SMAD-dependent signaling in non-small cell lung cancer Corrigendum in /10.3892/or.2020.7868

Yang,Haiping; Zhan,Lei; Yang,Tianjie; Wang,Longqiang; Li,Chang; Zhao,Jun; Lei,Zhe; Li,Xiangdong; Zhang,Hong-Tao

doi:10.3892/or.2015.3961

Ski prevents TGF-β-induced EMT and cell invasion by repressing SMAD-dependent signaling in non-small cell lung cancer

Corrigendum in: /10.3892/or.2020.7868

Authors:
- Haiping Yang
- Lei Zhan
- Tianjie Yang
- Longqiang Wang
- Chang Li
- Jun Zhao
- Zhe Lei
- Xiangdong Li
- Hong-Tao Zhang
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Affiliations: Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China, Suzhou Key Laboratory for Molecular Cancer Genetics, Suzhou, Jiangsu 215123, P.R. China, Department of Neurosurgery, The First Affiliated Hospital, Soochow University, Medical College of Soochow University, Suzhou, Jiangsu 215006, P.R. China
Published online on: May 7, 2015 https://doi.org/10.3892/or.2015.3961
Pages: 87-94

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Abstract

Epithelial-mesenchymal transition (EMT) is a key event in cancer metastasis, which confers cancer cells with increased motility and invasiveness, and EMT is characterized by loss of epithelial marker E-cadherin and gain of mesenchymal marker N-cadherin. Transforming growth factor-β (TGF-β) signaling is a crucial inducer of EMT in various types of cancer. Ski is an important negative regulator of TGF-β signaling, which interacts with SMADs to repress TGF-β signaling activity. Although there is accumulating evidence that Ski functions as a promoter or suppressor in human types of cancer, the molecular mechanisms by which Ski affects TGF-β-induced EMT and invasion in non-small cell lung cancer (NSCLC) are not largely elucidated. In the present study, we investigated the mechanistic role of Ski in NSCLC metastasis. Ski was significantly reduced in metastatic NSCLC cells or tissues when compared with non-metastatic NSCLC cells or tissues. Moreover, following TGF-β stimulation Ski-silenced A549 cells had more significant features of EMT and a higher invasive activity when compared with A549 cells overexpressing Ski. Mechanistically, Ski-silenced and overexpressed A549 cells showed an increase and a reduction in the SMAD3 phosphorylation level, respectively. This was supported by plasminogen activator inhibitor-1 (PAI-1) promoter activity obtained in Ski-silenced and overexpressed A549 cells. However, after treatment of SIS3 (inhibitor of SMAD3 phosphorylation) followed by TGF-β1 stimulation, we did not observe any effect of Ski on TGF-β-induced EMT, and invasion in Ski-silenced and overexpressed A549 cells. In conclusion, our findings suggest that Ski represses TGF-β-induced EMT and invasion by inhibiting SMAD-dependent signaling in NSCLC.

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