title: Arf6 regulates EGF-induced internalization of E-cadherin in breast cancer cells.
abstract: E-cadherin internalization facilitates dissolution of adherens junctions and promotes tumor cell epithelial-mesenchymal transition (EMT) and migration. Our previous results have shown that Arf6 exerts pro-migratory action in breast cancer cells after EGF stimulation. Despite the fact that EGF signaling stimulates EMT of breast cancer cells, the effect of Arf6 on internalization of E-cadherin of breast cancer cells under EGF treatment remains to be determined. Here, we showed that EGF dose-dependently stimulated E-cadherin internalization by MCF-7 cells with the maximal effect at 50 ng/ml. Meanwhile, EGF treatment markedly increased Arf6 activation. Arf6 was involved in complexes of E-cadherin, and more E-cadherin was pulled down with Arf6 when the activity of the latter was increased. Immunoblotting and immunofluorescence assays showed that transfection breast cancer cells with Arf6-T27N or Arf6 siRNA suppressed EGF-induced E-cadherin internalization. Taken together, our study demonstrated that Arf6 activation plays a potential role in EGF-induced E-cadherin internalization, providing new mechanism underlying the effect of Arf6 on promoting breast cancer cell metastasis.
authors: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029 China ; Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029 China ; Department of Biotechnology, Nanjing Medical University, Nanjing, Jiangsu 210029 China.
authors: Rui
authors: R
authors: Xu
authors: Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029 China ; Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu 210029 China.
authors: Yujie
authors: Y
authors: Zhang
authors: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029 China ; Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029 China.
authors: Luo
authors: L
authors: Gu
authors: Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029 China.
authors: Jianchao
authors: J
authors: Zheng
authors: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu 210029 China.
authors: Jie
authors: J
authors: Cui
authors: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu 210029 China ; Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, Nanjing Medical University, Nanjing, Jiangsu 210029 China.
authors: Jing
authors: J
authors: Dong
authors: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029 China ; Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029 China.
authors: Jun
authors: J
authors: Du
keywords: Arf6; Breast cancer; E-cadherin; EGF; Internalization