Cell membrane gp96 facilitates HER2 dimerization and serves as a novel target in breast cancer |
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| Authors: | Xin Li Lu Sun Junwei Hou Mingming Gui Jianming Ying Hong Zhao Ning Lv Songdong Meng |
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| 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 |
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| 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. |
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| Keywords: | breast cancer grp94 cell membrane gp96 HER2 dimerization targeted therapy |
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