Fibronectin induces epithelial-mesenchymal transition in human breast cancer MCF-7 cells via activation of calpain

Li,Cheng‑Lin; Yang,Dan; Cao,Xin; Wang,Fan; Hong,Duan‑Yang; Wang,Jing; Shen,Xiang‑Chun; Chen,Yan

doi:10.3892/ol.2017.5896

Fibronectin induces epithelial-mesenchymal transition in human breast cancer MCF-7 cells via activation of calpain

Authors:
- Cheng‑Lin Li
- Dan Yang
- Xin Cao
- Fan Wang
- Duan‑Yang Hong
- Jing Wang
- Xiang‑Chun Shen
- Yan Chen
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Affiliations: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Jiangsu Center for The Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China, Key Laboratory of Optimal Utilization of Natural Medicine Resources, Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China
Published online on: March 23, 2017 https://doi.org/10.3892/ol.2017.5896
Pages: 3889-3895

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Abstract

Fibronectin (FN) is a primary component of the mammary mesenchymal compartment and undergoes dramatic changes during breast cancer development. Increased FN expression is associated with an invasive and metastatic breast cancer phenotype. The present study demonstrated that FN causes an epithelial‑mesenchymal transition (EMT)‑like morphological change in MCF‑7 breast cancer cells. FN stimulation caused the downregulation of epithelial markers E‑cadherin and tight junction protein ZO‑1, and the upregulation of mesenchymal markers N‑cadherin and vimentin. Additionally, FN promoted cell migration and invasion in MCF‑7 cells, with increased expression of calpain‑2 and proteolysis of focal adhesion kinase 1 (FAK), indicating calpain activation. Notably, the FN induced changes in morphology and EMT markers were reversed with the treatment of calpain-specific inhibitors, calpain inhibitor I (N-acetyl-L‑leucyl-L-leucyl-L-norleucinal), calpeptin and calpain inhibitor IV. Meanwhile, the effects of FN on cell migration and invasion, as well as FAK proteolysis were markedly suppressed by calpain inhibitors. Taken together, the results of the present study indicate that calpain plays an essential role in FN-induced EMT response, and that targeting calpain signaling may be a potential strategy to reduce breast cancer metastasis.

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