title: Role of Erbin in ErbB2-dependent breast tumor growth.
abstract: ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2), a receptor tyrosine kinase of the ErbB family, is overexpressed in around 25% of breast cancers. In addition to forming a heterodimer with other ErbB receptors in response to ligand stimulation, ErbB2 can be activated in a ligand-independent manner. We report here that Erbin, an ErbB2-interacting protein that was thought to act as an antitumor factor, is specifically expressed in mammary luminal epithelial cells and facilitates ErbB2-dependent proliferation of breast cancer cells and tumorigenesis in MMTV-neu transgenic mice. Disruption of their interaction decreases ErbB2-dependent proliferation, and deletion of the PDZ domain in Erbin hinders ErbB2-dependent tumor development in MMTV-neu mice. Mechanistically, Erbin forms a complex with ErbB2, promotes its interaction with the chaperon protein HSP90, and thus prevents its degradation. Finally, ErbB2 and Erbin expression correlates in human breast tumor tissues. Together, these observations establish Erbin as an ErbB2 regulator for breast tumor formation and progression.
authors.affiliation: Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912; Key Lab of Organ Development and Regeneration of Zhejiang Province, Institute of Developmental and Regenerative Biology, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036, China;
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912; cshen@gru.edu jean-paul.borg@inserm.fr lmei@gru.edu.
authors.forename: Chengyong
authors.initials: C
authors.lastname: Shen
authors.affiliation: Center for Experimental Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, China; Institute of Life Sciences, Nanchang University, Jiangxi 330006, China;
authors.forename: Shiwen
authors.initials: S
authors.lastname: Luo
authors.affiliation: Cancer Research Center of Marseille, Cell Polarity, Cell Signalling and Cancer "Equipe labellisée Ligue Contre le Cancer," INSERM U1068, F-13009 Marseille, France; Institut Paoli-Calmettes, F-13009 Marseille, France; Aix-Marseille Université, F-13284 Marseille, France; and CNRS UMR7258, F-13009 Marseille, France.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Traoré
authors.affiliation: Cancer Research Center of Marseille, Cell Polarity, Cell Signalling and Cancer "Equipe labellisée Ligue Contre le Cancer," INSERM U1068, F-13009 Marseille, France; Institut Paoli-Calmettes, F-13009 Marseille, France; Aix-Marseille Université, F-13284 Marseille, France; and CNRS UMR7258, F-13009 Marseille, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Marchetto
authors.affiliation: Cancer Research Center of Marseille, Cell Polarity, Cell Signalling and Cancer "Equipe labellisée Ligue Contre le Cancer," INSERM U1068, F-13009 Marseille, France; Institut Paoli-Calmettes, F-13009 Marseille, France; Aix-Marseille Université, F-13284 Marseille, France; and CNRS UMR7258, F-13009 Marseille, France.
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Santoni
authors.affiliation: Center for Experimental Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, China;
authors.forename: Linlin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Center for Experimental Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, China;
authors.forename: Biao
authors.initials: B
authors.lastname: Wu
authors.affiliation: Center for Experimental Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, China;
authors.forename: Chao
authors.initials: C
authors.lastname: Shi
authors.affiliation: Center for Experimental Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, China;
authors.forename: Jinghong
authors.initials: J
authors.lastname: Mei
authors.affiliation: Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912;
authors.forename: Ryan
authors.initials: R
authors.lastname: Bates
authors.affiliation: Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912;
authors.forename: Xihui
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912;
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912;
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Xiong
authors.affiliation: Cancer Research Center of Marseille, Cell Polarity, Cell Signalling and Cancer "Equipe labellisée Ligue Contre le Cancer," INSERM U1068, F-13009 Marseille, France; Institut Paoli-Calmettes, F-13009 Marseille, France; Aix-Marseille Université, F-13284 Marseille, France; and CNRS UMR7258, F-13009 Marseille, France cshen@gru.edu jean-paul.borg@inserm.fr lmei@gru.edu.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Borg
authors.affiliation: Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912; Institute of Life Sciences, Nanchang University, Jiangxi 330006, China; cshen@gru.edu jean-paul.borg@inserm.fr lmei@gru.edu.
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009154:Mutation; D011485:Protein Binding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D018841:HSP90 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C413364:ERBIN protein, human; C498804:Erbb2ip protein, mouse; C508053:ERBB2 protein, human; C524056:Erbb2 protein, mouse
keywords: ErbB2; Erbin; HSP90; breast cancer; stability