Simultaneous stimulation with tumor necrosis factor-α and transforming growth factor-β1 induces epithelial-mesenchymal transition in colon cancer cells via the NF-κB pathway

Li,Yuanfei; Zhu,Guoqiang; Zhai,Huihong; Jia,Junmei; Yang,Wenhui; Li,Xiaoqing; Liu,Lixin

doi:10.3892/ol.2018.8230

Simultaneous stimulation with tumor necrosis factor-α and transforming growth factor-β1 induces epithelial-mesenchymal transition in colon cancer cells via the NF-κB pathway

Authors:
- Yuanfei Li
- Guoqiang Zhu
- Huihong Zhai
- Junmei Jia
- Wenhui Yang
- Xiaoqing Li
- Lixin Liu
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Affiliations: Department of Oncology, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Burns and Plastic Surgery, The 264th Hospital of the PLA, Taiyuan, Shanxi 030001, P.R. China, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China, Department of Gastroenterology and Hepatology, The First Clinical Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
Published online on: March 12, 2018 https://doi.org/10.3892/ol.2018.8230
Pages: 6873-6880
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Epithelial-mesenchymal transition (EMT) is critical in the progression of numerous types of carcinoma, and endows invasive and metastatic properties upon cancer cells. The tumor microenvironment facilitates tumor metastasis to distant organs. Various signaling pathways contribute to this process. In the present study, SW480 colon adenocarcinoma cells were treated with transforming growth factor-β1 (TGF‑β1; 10 ng/ml) and tumor necrosis factor-α (TNF‑α; 20 ng/ml), alone or in combination, for 72 h, and EMT was assessed using immunofluorescence, western blot analysis and migration assays. The functions of p38 mitogen‑activated protein kinase, extracellular signal‑regulated kinase (ERK) and nuclear factor-κB (NF‑κB) pathways in EMT were examined. It was demonstrated that the cooperation of TGF‑β1 and TNF‑α signaling promoted the morphological conversion of the SW480 cells from an epithelial to a mesenchymal phenotype. Furthermore, simultaneous exposure to TNF‑α and TGF‑β1 downregulated the expression of E‑cadherin (an epithelial marker) and increased the expression of N‑cadherin and vimentin (mesenchymal markers). Additionally, the migratory capacity of the SW480 cells increased. The inhibition of p38 and ERK signaling exhibited no effect on EMT, whereas the inhibition of inhibitor of NF‑κB kinase subunit β blocked the EMT induced by TGF‑β1 and TNF‑α. In conclusion, the results of the present study demonstrated that TNF‑α and TGF‑β1 synergistically promoted EMT in SW480 cells via the NF‑κB pathway, independent of p38 activation and ERK1/2 signaling. These results suggest a novel function of TGF‑β1 and TNF‑α during EMT in colon carcinoma and, thus, provide insights into potential therapeutic interventions.

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