p62 participates in the inhibition of NF-κB signaling and apoptosis induced by sulfasalazine in human glioma U251 cells

Abstract

Nuclear factor-κB (NF-κB) is constitutively activated in most malignant gliomas and is involved in cancer progression and drug resistance to chemotherapy. Sulfasalazine (SAS) is a classic inhibitor of NF-κB. Apoptosis and autophagy were induced by SAS accompanied by inhibition of NF-κB signaling in U251 cells. Inhibition of autophagy by 3-MA suppressed the effects of SAS on NF-κB signaling and apoptosis in U251 cells. Multifunctional scaffold protein p62 is well known as an autophagy marker protein and provides crosstalk for important signaling pathways, including NF-κB signaling. SAS-induced decrease in the p62 protein levels may be the result of degradation through autophagy. SAS induced the inhibition of NF-κB signaling and apoptosis at least partly via a p62-dependent effect in U251 cells. Collectively, our data shed light on the link between p62 and the NF-κB signaling pathway, particularly in glioma cells. The results may facilitate the design of more effective targeted therapies for the treatment of tumors in which NF-κB signaling is altered.

RETRACTED: Inflammatory-Related P62 Triggers Malignant Transformation of Mesenchymal Stem Cells through the Cascade of CUDR-CTCF-IGFII-RAS Signaling

“…The P62 knockdown coordinates a series of antiproliferative responses and may facilitate dedifferentiation of mature hepatocytes into nestin-positive progenitor-like cells. 23 , 24 Herein, our results showed that P62 cooperates with TNF-α to promote the malignant transformation of mesenchymal stem cells. The involvement of promotion of the malignant transformation of mesenchymal stem cells is supported by results from two parallel sets of experiments: (1) P62 triggers mesenchymal stem cells’ malignant transformation in injury inflammatory mouse liver and (2) excessive P62 cooperates with TNF-α to accelerate mesenchymal stem cells’ malignant growth in vitro and in vivo.…”

Pan-Bcl-2 inhibitor Obatoclax is a potent late stage autophagy inhibitor in colorectal cancer cells independent of canonical autophagy signaling

“…P62 is a scaffold protein involved in a variety of cellular processes including NF-kB-signaling [ 31 , 50 , 51 ]. Recently, a correlation of p62 expression with clinicopathologic parameters has been shown for prostate cancer and gastrointestinal carcinoma [ 52 , 53 ].…”

Life, death, and autophagy in cancer: NF-κB turns up everywhere

“…Accordingly, p62 knockdown reduced both the proliferation of cancer cells and tumor growth. Although the regulation of mitochondrial integrity by mitophagy seems to be the principal mechanism by which p62 promotes cancer cell survival, it remains to be clarified the impact of p62 in the regulation of important signaling pathway in cancer, such as NF-κΒ 60,77,[79][80][81] . p62 alters IKK/NF-κΒ signaling by promoting IκΒα phosphorylation and its autophagy-dependent degradation 20,82,83 .…”