title: Cell membrane gp96 facilitates HER2 dimerization and serves as a novel target in breast cancer.
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.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Hou
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Gui
authors.affiliation: Chinese Academy of Medical Sciences, Cancer Institute and Hospital, Beijing, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Ying
authors.affiliation: Chinese Academy of Medical Sciences, Cancer Institute and Hospital, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Chinese Academy of Medical Sciences, Cancer Institute and Hospital, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Lv
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Songdong
authors.initials: S
authors.lastname: Meng
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D064596:Isografts; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D055503:Protein Multimerization; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D047368:Tumor Burden
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C053387:endoplasmin
keywords: HER2 dimerization; breast cancer; cell membrane gp96; grp94; targeted therapy