title: Differential role of psoriasin (S100A7) in estrogen receptor α positive and negative breast cancer cells occur through actin remodeling.
abstract: Psoriasin (S100A7) is a calcium-binding protein that has shown to be highly expressed in high-grade ductal carcinoma in situ (DCIS) and a subset of invasive breast cancers. However, its role in invasion and metastasis is not very well known. In this study, we have shown that S100A7 differentially regulates epidermal growth factor (EGF)-induced cell migration and invasion in ERα(-) MDA-MB-231 cells and ERα(+) MCF-7 and T47D breast cancer cells. Further signaling studies revealed that S100A7 enhances EGF-induced EGFR phosphorylation and actin remodeling that seems to favor lamellipodia formation in ERα(-) cells. In addition, S100A7 overexpression enhanced NF-κB-mediated matrix metalloproteinase-9 (MMP-9) secretion in MDA-MB-231 cells indicating its role in enhanced invasiveness. However, S100A7 overexpression inhibited migration and invasion of MCF-7 cells by inactivating Rac-1 pathway and MMP-9 secretion. Moreover, S100A7 overexpressing MDA-MB-231 cells showed enhanced metastasis compared to vector control in in vivo nude mice as detected by bioluminescence imaging. Our tissue microarray data also revealed predominant expression of S100A7 in ERα(-) metastatic carcinoma, especially in lymph node regions. Overall these studies suggest that S100A7 may enhance metastasis in ERα(-) breast cancer cells by a novel mechanism through regulation of actin cytoskeleton and MMP-9 secretion.
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Amita
authors.initials: A
authors.lastname: Sneh
authors.forename: Yadwinder S
authors.initials: YS
authors.lastname: Deol
authors.forename: Akaansha
authors.initials: A
authors.lastname: Ganju
authors.forename: Konstantin
authors.initials: K
authors.lastname: Shilo
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Rosol
authors.forename: Mohd W
authors.initials: MW
authors.lastname: Nasser
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ganju
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D008163:Luminescent Measurements; D008198:Lymph Nodes / Q000378:metabolism; D008207:Lymphatic Metastasis; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000378:metabolism*; D015398:Signal Transduction; D046888:Tissue Array Analysis; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D016328:NF-kappa B; C107953:RAC1 protein, human; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D020780:Matrix Metalloproteinase 9; D020830:rac1 GTP-Binding Protein
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