title: S100A14, a member of the EF-hand calcium-binding proteins, is overexpressed in breast cancer and acts as a modulator of HER2 signaling.
abstract: HER2 is overexpressed in 20–25% of breast cancers. Overexpression of HER2 is an adverse prognostic factor and correlates with decreased patient survival. HER2 stimulates breast tumorigenesis via a number of intracellular signaling molecules, including PI3K/AKT and MAPK/ERK.S100A14,one member of the S100 protein family, is significantly associated with outcome of breast cancer patients. Here, for the first time, we show that S100A14 and HER2 are coexpressed in invasive breast cancer specimens,andthere is a significant correlation between the expression levels of the two proteins by immunohistochemistry. S100A14 and HER2 are colocalized in plasma membrane of breast cancer tissue cells and breast cancer cell lines BT474 and SK-BR3. We demonstrate that S100A14 binds directly to HER2 by co-immunoprecipitation and pull-down assays. Further study shows that residues 956–1154 of the HER2 intracellular domain and residue 83 of S100A14 are essential for the two proteins binding.Moreover,we observe a decrease of HER2 phosphorylation, downstream signaling, and HER2-stimulated cell proliferation in S100A14-silenced MCF-7, BT474, and SK-BR3 cells. Our findings suggest that S100A14 functions as a modulator of HER2 signaling and provide mechanistic evidence for its role in breast cancer progression.
authors.affiliation: From the State Key Laboratory of Molecular Oncology.
authors.forename: Chengshan
authors.initials: C
authors.lastname: Xu
authors.forename: Hongyan
authors.initials: H
authors.lastname: Chen
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.forename: Jidong
authors.initials: J
authors.lastname: Gao
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Che
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Ding
authors.forename: Aiping
authors.initials: A
authors.lastname: Luo
authors.forename: Shuguang
authors.initials: S
authors.lastname: Zhang
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Liu
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D020832:EF Hand Motifs / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D008875:Middle Aged; D011485:Protein Binding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D002135:Calcium-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C462950:S100A14 protein, human
keywords: Breast Cancer; Cell Proliferation; Protein Phosphorylation; Protein-Protein Interactions; S100 Proteins