NFE2L2 overexpression

Additionally, USP13 depletion promotesan autophagy-to-ferroptosis switch invitro andin xenograft tumor mouse models, through the activation of theNFE2L2-SQSTM1/p62 (sequestosome 1)-KEAP1 axis in KRAS mutant cellsand tumor tissues. Hence, targeting USP13 effectively switchedautophagy-to-ferroptosis, thereby inhibiting KRAS (KRASproto-oncogene, GTPase) mutant LUAD, suggesting the therapeuticpromise of combining autophagy and ferroptosis in the KRAS-mutantLUAD.

Mechanistically, Nrf2 is involved in cell cycle abnormalities induced by prolonged exposure to HQ by binding to p16, thereby activating the p16/Rb signaling pathway. Taken together, Nrf2 might be a potential driver of carcinogenesis that promotes malignant cell proliferation and affects cell cycle distribution.

In glioma, especially GBM, there is a strong association between gene expression and immune infiltration, even in macrophages, nTreg, and Th2 cells, which play immunosuppressive functions in TME. In conclusion, these results indicate that NFE2L2 and NOX4 could be risk prognosis biomarkers in glioma, and they bound up with immune infiltration and tumor immunity in tumorigenesis.

At the post-translational level, the proteasome inhibitor MG132, but not the lysosomal inhibitors ammonium chloride and bafilomycin, prevented the hypoxic depletion of p62, suggesting the involvement of the proteasome pathway...We concluded that a decrease in p62, which involves regulation at the transcriptional and post-translational levels, is critical for cell survival under hypoxia. The present results show the potential of targeting Nrf2/Parkin-Hsc70-p62 as a novel strategy to eradicate hypoxic solid tumors.

In vivo data suggested that vinpocetine (50 mg/kg) inhibited tumor growth and enhanced the antitumor effects of cisplatin in the NSCLC cell tumor-bearing model. Vinpocetine enhances cisplatin sensitivity of NSCLC cells in part by suppressing Nrf2 signaling.

The finding that tumorigenesis can be driven by any two arms of the β-catenin/Hippo/NFE2L2 axis has permitted the identification of a small subset of coordinately regulated tumor-specific transcripts, some of whose levels correlate with inferior long-term outcomes in HB and other cancers. Collectively, these findings begin to provide for more refined and molecularly based classification, survival algorithms and design of chemotherapeutic regimens.

NFE2L2 mutation has a very significant correlation with higher TMB and MSI, but not related to PD-L1 expression . However, whether NFE2L2-MT is related to the efficacy of immunotherapy was still unclear and more clinical data were needed.