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01-04-2020 | Breast Cancer | Original Article

CUL1 Knockdown Attenuates the Adhesion, Invasion, and Migration of Triple-Negative Breast Cancer Cells via Inhibition of Epithelial-Mesenchymal Transition

Authors: Ze-Qiang Ren, Wen-Jing Yan, Xiu-Zhong Zhang, Peng-Bo Zhang, Chong Zhang, Shou-Kun Chen

Published in: Pathology & Oncology Research | Issue 2/2020

Abstract

Cullin-1 (CUL1) is an important factor for tumor growth and a potential therapeutic target for breast cancer therapy, but the molecular mechanism in triple-negative breast cancer (TNBC) is unknown. In the present study, CUL1 shRNA was transfected into BT549 and MDA-MB-231 breast cancer cells. Cell morphology, adhesion, invasion, and migration assays were carried out in the CUL1 knockdown cells. Additionally, protein expression levels of epithelial-mesenchymal transition (EMT)-related factors, Akt phosphorylation at S473 (pAkt), glycogen synthase kinase-3β phosphorylation at ser9 (pGSK3β), cytoplasmic and nuclear β-catenin, and epidermal growth factor receptor phosphorylation at Tyr1068 (pEGFR) were detected by Western blot analysis. CUL1 knockdown significantly suppressed the adhesion, invasion and migration capabilities of the cells, and decreased the expression of Snail1/2, ZEB1/2, Twist1/2, Vimentin, and increased the expression of Cytokeratin 18 (CK18). Moreover, CUL1 knockdown significantly downregulated the phosphorylated levels of Akt, GSK3β, and EGFR, inhibiting the translocation of β-catenin from the cytoplasm to the nucleus. The results indicate that CUL1 knockdown prohibited the metastasis behaviors of breast cancer cells through downregulation (dephosphorylation) of the EMT signaling pathways of EGFR and Akt/GSK3β/β-catenin in breast cancer. These results strongly suggested that reinforcement of the EMT might be a key for CUL1 to accelerate TNBC metastasis.

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Title: CUL1 Knockdown Attenuates the Adhesion, Invasion, and Migration of Triple-Negative Breast Cancer Cells via Inhibition of Epithelial-Mesenchymal Transition
Authors: Ze-Qiang Ren
Wen-Jing Yan
Xiu-Zhong Zhang
Peng-Bo Zhang
Chong Zhang
Shou-Kun Chen
Publication date: 01-04-2020
Publisher: Springer Netherlands
Keywords: Breast Cancer
Breast Cancer
Published in: Pathology & Oncology Research / Issue 2/2020
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-019-00681-6

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