title: N-cadherin promotes epithelial-mesenchymal transition and cancer stem cell-like traits via ErbB signaling in prostate cancer cells.
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.
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Ren
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Qiji
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pathology, The First People's Hospital of Guangzhou City, Guangzhou, Guangdong 510180, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Du
authors.affiliation: State Key Laboratory of Oncology in Southern China/Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Libing
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Peng
mesh_terms: D015820:Cadherins / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D051380:GRB2 Adaptor Protein / Q000235:genetics; D006801:Humans; D000090062:Kruppel-Like Factor 4; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D018739:Oncogene Proteins v-erbB / Q000235:genetics*; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics*; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015820:Cadherins; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D018739:Oncogene Proteins v-erbB; D055765:Shc Signaling Adaptor Proteins; D014157:Transcription Factors