title: Interaction Between Ezrin and Cortactin in Promoting Epithelial to Mesenchymal Transition in Breast Cancer Cells.
abstract: BACKGROUND Epithelial to mesenchymal transition (EMT) contributes to metastases in various types of tumors, and is also the key step in the breast cancer metastatic cascade. In our previous study, a mouse model containing human-derived normal breast tissue was established and allowed EMT/MET process of human breast cancer cells to be mimicked in a humanized mammary microenvironment. MATERIAL AND METHODS Two-dimensional electrophoresis (2-DE) and mass spectrometry were used to detect different proteins between parental MDA-MB-231 and its variant sub-line obtained from tumors grown in transplanted normal human breast tissue (MDA-MB-231br). We knocked down the ezrin in 2 cell lines (MDA-MB-231 and SUM1315). The migration and invasion ability was assessed. EMT markers were examined by real-time reverse transcription PCR analysis and Western blot analysis. The relationship of ezrin with cortactin was tested by tissue microarray and co-immunoprecipitation. RESULTS Proteomic analysis revealed 81 differentially expressed proteins between parental MDA-MB-231 and MDA-MB-231br. Among these proteins, the expression of ezrin and cortactin and the phosphorylation of ezrin were significantly correlated, accompanied with a group of classic EMT makers. Knockdown of ezrin reversed the expression of EMT markers and downregulated cortactin and EMT transcription factors. Ezrin silencing inhibited tumor cell migration and invasion. Breast cancer tissue microarray and immunohistochemistry showed a significant positive association between ezrin and cortactin. CONCLUSIONS These findings indicate that ezrin is correlated with cortactin in facilitating EMT in breast cancer. The interaction between ezrin and cortactin is a novel mechanism contributing to the EMT process in cancer metastases.
authors.affiliation: Department of Surgical Oncology, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China (mainland).
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.affiliation: Breast Disease Center, 1st Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China (mainland).
authors.forename: Ge
authors.initials: G
authors.lastname: Ma
authors.affiliation: Breast Disease Center, 1st Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China (mainland).
authors.forename: Jiayi
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China (mainland).|State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China (mainland).
authors.forename: Yichao
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Breast Disease Center, 1st Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China (mainland).
authors.forename: Mengdi
authors.initials: M
authors.lastname: Liang
authors.affiliation: Breast Disease Center, 1st Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China (mainland).
authors.forename: Na
authors.initials: N
authors.lastname: Yao
authors.affiliation: Breast Disease Center, 1st Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China (mainland).
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Breast Disease Center, 1st Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China (mainland).
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Breast Disease Center, 1st Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China (mainland).
authors.forename: Xiaoan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Breast Disease Center, 1st Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China (mainland).
authors.forename: Tiansong
authors.initials: T
authors.lastname: Xia
authors.affiliation: Breast Disease Center, 1st Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China (mainland).
authors.forename: Shui
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D051356:Cortactin / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D011379:Prognosis; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D000099149:Ezrin
chemical_list: D051356:Cortactin; D003598:Cytoskeletal Proteins; D014157:Transcription Factors; D000099149:Ezrin