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Cell membrane gp96 facilitates HER2 dimerization and serves as a novel target in breast cancer
Authors:Xin Li  Lu Sun  Junwei Hou  Mingming Gui  Jianming Ying  Hong Zhao  Ning Lv  Songdong Meng
Affiliation:1. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China;2. Chinese Academy of Medical Sciences, Cancer Institute and Hospital, Beijing, China
Abstract:HER2 receptor dimerization is a critical step in the HER2 activation process. Here, we demonstrated that heat shock protein gp96 on cell membrane interacts with HER2, facilitates HER2 dimerization and promotes cell proliferation. Cell membrane gp96 levels were observed to correlate with HER2 phosphorylation in primary breast tumors. Finally, we provide evidence that targeting gp96 with a specific monoclonal antibody led to decreased cell growth and increased apoptosis in vitro, and suppression of tumor growth in vivo. Our work represents a new therapeutic strategy for inhibiting HER2 signaling in cancer.
Keywords:breast cancer  grp94  cell membrane gp96  HER2 dimerization  targeted therapy
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