s100a7-downregulation inhibits epidermal growth factor-induced signaling in breast cancer cells and blocks osteoclast formations100a7-downregulation抑制表皮生长因素在乳腺癌细胞信号和块破骨细胞的形成.pdfVIP

S100A7-Downregulation Inhibits Epidermal Growth Factor-Induced Signaling in Breast Cancer Cells and Blocks Osteoclast Formation 1 1 2 3 4 1 Vikram Paruchuri , Anil Prasad , Kevin McHugh , Hari K. Bhat , Kornelia Polyak , Ramesh K. Ganju * 1 Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America, 3 Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, United States of America, 4 Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States of America Abstract S100A7 is a small calcium binding protein, which has been shown to be differentially expressed in psoriatic skin lesions, as well as in squamous cell tumors of the skin, lung and breast. Although its expression has been correlated to HER+ high- grade tumors and to a high risk of progression, the molecular mechanisms of these S100A7-mediated tumorigenic effects are not well known. Here, we showed for the first time that epidermal growth factor (EGF) induces S100A7 expression in both MCF-7 and MDA-MB-468 cell lines. We also observed a decrease in EGF-directed migration in shRNA-downregulated MDA-MB-468 cell lines. Furthermore, our signaling studies revealed that EGF induced simultaneous EGF receptor phosphorylation at Tyr1173 and HER2 phosphorylation at Tyr1248 in S100A7-downregulated cell lines as compared to the vector-transfected controls. In addition, reduced phosphorylation of Src at tyrosine 416 and p-SHP2 at tyrosine 542