title: Regulation of anoikis by deleted in breast cancer-1 (DBC1) through NF-κB.
abstract: Anoikis-resistance of tumor cells is critical for anchorage-independent growth and metastasis. The inflammatory-response transcription factor NF-κB contributes to anoikis-resistance and tumor progression through mechanisms that are understood incompletely. Deleted in breast cancer-1 (DBC1) protein (KIAA1967) is over-expressed in several tumor types, and correlates with a poorer prognosis in some cases. We report here that DBC1 suppressed anoikis in normal epithelial and breast cancer cell lines. DBC1 interacted with IKK-β, stimulating its kinase activity, promoting NF-κB transcriptional activity through the phosphorylation of relA serine-536 and enhancing the expression of the NF-κB target genes, c-FLIP and bcl-xl. Our results indicate that DBC1 is an important co-factor for the control of the IKK-β-NF-κB signaling pathway that regulates anoikis.
authors.affiliation: Mary Babb Randolph Cancer Center, West Virginia University, 1 Medical Center Drive, Campus, Room 2833, Morgantown, WV 26506, USA.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Park
authors.forename: Philip
authors.initials: P
authors.lastname: Riley
authors.forename: Steven M
authors.initials: SM
authors.lastname: Frisch
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D023102:Anoikis; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C527450:CCAR2 protein, human; D016328:NF-kappa B; D051996:Transcription Factor RelA; D051550:I-kappa B Kinase