N-cadherin promotes epithelial-mesenchymal transition and cancer stem cell-like traits via ErbB signaling in prostate cancer cells

Wang,Min; Ren,Dong; Guo,Wei; Huang,Shuai; Wang,Zeyu; Li,Qiji; Du,Hong; Song,Libing; Peng,Xinsheng

doi:10.3892/ijo.2015.3270

N-cadherin promotes epithelial-mesenchymal transition and cancer stem cell-like traits via ErbB signaling in prostate cancer cells

Authors:
- Min Wang
- Dong Ren
- Wei Guo
- Shuai Huang
- Zeyu Wang
- Qiji Li
- Hong Du
- Libing Song
- Xinsheng Peng
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Affiliations: Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Pathology, The First People's Hospital of Guangzhou City, Guangzhou, Guangdong 510180, P.R. China, State Key Laboratory of Oncology in Southern China/Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
Published online on: November 26, 2015 https://doi.org/10.3892/ijo.2015.3270
Pages: 595-606

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Abstract

N-cadherin has been reported to be upregulated and associated with metastasis and poor prognosis in prostate cancer patients, however the underlying mechanism still remains puzzling. In the present study, we found that upregulation of N-cadherin enhanced, while downregulation of N-cadherin impaired the invasion, migration, and epithelial to mesenchymal transition (EMT) of prostate cancer (PCa) cells. Overexpression of N-cadherin increased the efficiency of colony and tumor spheroid formation and the stemness factor expression (including c-Myc, Klf4, Sox2 and Oct4), and vice versa. Furthermore, microarray analysis and western blot analysis mechanistically proved that N-cadherin activated ErbB signaling pathway by upregulating the expression of Grb2, pShc and pERK1/2. Importantly, the regulation of N-cadherin on EMT and stemness was counteracted by lapatinib, a specific ErbB signaling pathway inhibitor. Collectively, these findings demonstrate that N-cadherin regulates EMT and stemness of PCa cells via activating ErbB signaling pathway, which indicates the pivotal role of N-cadherin/ErbB axis in the metastasis of prostate cancer.

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