Identification of ADAM10 as a major source of HER2 ectodomain sheddase activity in HER2 overexpressing breast cancer cells

ALL AUTHORS: Phillip C.C. Liu, Xiangdong Liu, Yanlong Li, Maryanne Covington, Richard Wynn, Reid Huber, Milton Hillman, Gengjie Yang, Dawn Ellis, Cindy Marando, Kamna Katiyar, Jodi Bradley, Kenneth Abremski, Mark Stow, Mark Rupar, Jincong Zhuo, Yun-Long Li, Qiyan Lin, David Burns, Meizhong Xu, Colin Zhang, Ding-Quan Qian, Chunhong He, Vaqar Sharief, Lingkai Weng, Costas Agrios, Eric Shi, Brian Metcalf, Robert Newton, Steven Friedman, Wenqing Yaol, Peggy Scherlel, Gregory Hollis, Timothy C. Burn Overexpression and activating mutations of ErbB family members have been implicated in the development and progression of a variety of tumor types. Cleavage of the HER2 receptor by an as yet unidentified ectodomain sheddase has been shown to liberate the HER2 extracellular domain (ECD) leaving a fragment with constitutive kinase activity that can provide ligand-independent growth and survival signals to the cell. This process is clinically relevant since HER2 ECD serum levels in metastatic breast cancer patients ar...