Elevated NIBP/TRAPPC9 mediates tumorigenesis of cancer cells through NFκB signaling

摘要: Regulatory mechanisms underlying constitutive and inducible NFκB activation in cancer remain largely unknown. Here we investigated whether a novel NIK- IKK2-binding protein (NIBP) is required for maintaining malignancy of cells an NFκB-dependent manner. Real-time polymerase chain reaction analysis human survey tissue-scan cDNA array, immunostaining frozen tumor tissue array immunoblotting high-density reverse-phase lysate showed that NIBP extensively expressed most tissues, particularly breast colon cancer. Lentivirus-mediated shRNA knockdown significantly inhibited the growth/proliferation, invasion/migration, colony formation xenograft tumorigenesis (MDA-MB-231) or (HCT116) cells. overexpression HCT116 promoted cell proliferation, migration formation. Mechanistically, cytokine-induced luciferase reporter, thus sensitizing to TNFα-induced apoptosis. Endogenous bound specifically phosphorylated IKK2 TNFα-dependent transiently attenuated TNFα-stimulated phosphorylation IKK2/p65 degradation IκBα. In contrast, enhanced activation, inhibiting Collectively, our data identified important roles promoting via NFκΒ signaling, spotlighting as promising target therapeutic intervention.