title: NF-κB affects proliferation and invasiveness of breast cancer cells by regulating CD44 expression.
abstract: NF-κB plays an important role in cancer initiation and progression. CD44, a cell surface glycoprotein, is involved in many cellular processes including cell adhesion, migration and proliferation. However, whether and how the two molecules interact in breast cancer is not clear. In recent years, the up-regulation of CD44 has served as a marker for tumor initiating cells in breast cancer and other cancer types. Despite the important role of CD44 in cellular processes and cancer, the mechanism underlying CD44 up-regulation in cancers remains poorly understood. Previously, we have identified a novel cis-element, CR1, located upstream of the CD44 promoter. We demonstrated that NF-κB and AP-1 are key trans-acting factors that interact with CR1. Here, we further analyzed the role of NF-κB in regulating CD44 expression in triple negative breast cancer cells, MDA-MB-231 and SUM159. Inhibition of NF-κB by Bay-11-7082 resulted in a reduction in CD44 expression. CD44 repression via NF-κB inhibition consequently decreased proliferation and invasiveness of breast cancer cells. These findings provide not only new insight into the molecular mechanism underlying CD44 regulation but also potential therapeutic targets that may help eliminate chemo- and radiation-resistant cancer cells.
authors.affiliation: Cell and Developmental Biology Graduate Program, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Smith
authors.affiliation: Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Yi Lisa
authors.initials: YL
authors.lastname: Lyu
authors.affiliation: Cell and Developmental Biology Graduate Program, Rutgers University, Piscataway, New Jersey, United States of America; Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Li
authors.initials: L
authors.lastname: Cai
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis*; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D016328:NF-kappa B; D009363:Neoplasm Proteins