Mary Babb Randolph Cancer Center, West Virginia University, 1 Medical Center Drive, Campus, Room 2833, Morgantown, WV 26506, USA.
Apoptosis. 2013 Aug;18(8):949-62. doi: 10.1007/s10495-013-0847-1.
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.
肿瘤细胞的抗失巢凋亡能力对于锚定非依赖性生长和转移至关重要。炎症反应转录因子 NF-κB 通过不完全了解的机制促进抗失巢凋亡和肿瘤进展。乳腺癌缺失基因 1（DBC1）蛋白（KIAA1967）在几种肿瘤类型中过表达，并且在某些情况下与预后较差相关。我们在这里报告 DBC1 抑制了正常上皮细胞和乳腺癌细胞系的失巢凋亡。DBC1 与 IKK-β 相互作用，刺激其激酶活性，通过磷酸化 relA 丝氨酸-536 促进 NF-κB 转录活性，并增强 NF-κB 靶基因 c-FLIP 和 bcl-xl 的表达。我们的结果表明，DBC1 是控制 IKK-β-NF-κB 信号通路的重要辅助因子，该信号通路调节失巢凋亡。
