title: Role of Wnt Co-Receptor LRP6 in Triple Negative Breast Cancer Cell Migration and Invasion.
abstract: The low-density lipoprotein receptor-related protein 6 (LRP6) is an essential Wnt co-receptor of the Wnt/β-catenin signaling pathway. Although studies have shown an increased expression of LRP6 in several types of cancer, its function in tumor development and progression remains to be elucidated. We herein demonstrated that LRP6 expression is up-regulated in human triple negative breast cancer (TNBC) patients and human TNBC cell lines, and that knockdown of LRP6 expression and treatment of recombinant Mesd protein (a specific inhibitor of LRP6) significantly decreased cell migration and invasion of TNBC MDA-MB-231 and BT549 cells. Interestingly, the effects of LRP6 knockdown and Mesd treatment on TNBC cell migration and invasion were more prominent than on TNBC cell proliferation/viability. Mechanistically, LRP6 knockdown and Mesd treatment inhibited Wnt/β-catenin signaling and decreased the expression of S100A4, a mediator of cancer metastasis and a specific target of Wnt/β-catenin signaling, in TNBC cells. Together, our data suggest that LRP6 promotes TNBC cell migration and invasion by regulating the expression and function of S100A4 via the Wnt/β-catenin signaling pathway. J. Cell. Biochem. 118: 2968-2976, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Radiation Oncology, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.|Drug Discovery Division, Department of Oncology, Southern Research Institute, Birmingham, Alabama, 35255.
authors.forename: Jinlu
authors.initials: J
authors.lastname: Ma
authors.affiliation: Drug Discovery Division, Department of Oncology, Southern Research Institute, Birmingham, Alabama, 35255.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Lu
authors.affiliation: Division of Preventive Medicine and Comprehensive Cancer Center, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Dongquan
authors.initials: D
authors.lastname: Chen
authors.affiliation: Drug Discovery Division, Department of Oncology, Southern Research Institute, Birmingham, Alabama, 35255.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: Drug Discovery Division, Department of Oncology, Southern Research Institute, Birmingham, Alabama, 35255.
authors.forename: Yonghe
authors.identifier: 0000-0002-3134-3319
authors.initials: Y
authors.lastname: Li
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C506348:MESD protein, human; D018832:Molecular Chaperones; D009363:Neoplasm Proteins
keywords: INVASION; LRP6; MESD; MIGRATION; S100A4; TNBC CELLS