Nerve Growth Factor Signaling Promotes Nuclear Translocation of TRAF4 to Enhance Tumor Stemness and Metastatic Dormancy Via C-Jun-mediated IL-8 Autocrine.

Tumor necrosis factor receptor-associated factor 4 (TRAF4), an E3 ubiquitin ligase, is frequently overexpressed in tumors. Although its cytoplasmic role in tumor progression is well-documented, the precise mechanisms underlying its nuclear localization and functional contributions in tumor cells remain elusive. This study demonstrated a positive correlation between the expression of nuclear TRAF4 and both tumor grades and stemness signatures in human cancer tissues.

Gambogic acid impairs the maintenance and therapeutic resistance of glioma stem cells by targeting B-cell-specific Moloney leukemia virus insert site 1.

Background: Glioblastoma (GBM) is the most common and lethal primary brain tumor with low effectiveness of available treatments. The tumor heterogeneity and therapeutic resistance are largely due to the presence of glioma stem cells (GSCs). Therefore, eliminating GSCs can overcome the progression, relapse, and resistance of GBM.

Inducing ubiquitination and degradation of TrxR1 protein by LW-216 promotes apoptosis in non-small cell lung cancer via triggering ROS production.

Thioredoxin reductases are frequently overexpressed in various solid tumors as a protective mechanism against heightened oxidative stress. Inhibitors of this system, such as Auranofin, are effective in eradicating cancer cells. However, the clinical significance of thioredoxin reductase 1 (TrxR1) in lung cancer, as well as the potential for its antagonist as a treatment option, necessitated further experimental validation.

ALDOA maintains NLRP3 inflammasome activation by controlling AMPK activation.

ALDOA: aldolase A; AMPK: AMP-activated protein kinase; ATG: autophagy related; ATG5: autophagy related 5; ATP: adenosine triphosphate; BMDMs: bone marrow-derived macrophages; CALCOCO2: calcium binding and coiled-coil domain 2; CASP1: caspase 1; CQ: chloroquine; FOXO3: forkhead box O3; IL1B: interleukin 1 beta; LPS: lipopolysaccharide; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MT: mutant; mtDNA: mitochondrial DNA; MTORC1: mechanistic target of rapamycin kinase complex 1; mtROS: mitochondrial reactive oxygen species; NLRP3: NLR family, pyrin domain containing 3; OPTN: optineurin; PBS: phosphate-buffered saline; PRKN/Parkin: parkin RBR E3 ubiquitin protein ligase; SN: supernatant; SQSTM1/p62: sequestosome 1; STK11/LKB1: serine/threonine kinase 11; TOMM20: translocase of outer mitochondrial membrane 20; ULK1: unc-51 like autophagy activating kinase 1; v-ATPase: vacuolar type H+-ATPase; WT: wild-type.

Inhibition of Pim-2 kinase by LT-171-861 promotes DNA damage and exhibits enhanced lethal effects with PARP inhibitor in multiple myeloma.

Multiple myeloma (MM) is a malignancy of antibody-producing plasma cells with genomic instability and genetic abnormality as its two hallmarks. Therefore, DNA damage is pervasive in MM cells, which indicates irregular DNA damage response (DDR) pathway. In this study, we demonstrated that LT-171-861, a multiple kinase inhibitor, could inhibit proliferation and induce apoptosis in MM cells.

Oroxylin A maintains the colonic mucus barrier to reduce disease susceptibility by reconstituting a dietary fiber-deprived gut microbiota.

Dietary fiber intake helps to maintain gut homeostasis. Fiber deficiency causes commensals to utilize mucins as an energy source to destroy mucus layer, thus promoting susceptibility to inflammatory bowel disease. Here, we reported that oroxylin A, a natural flavonoid, ameliorated low-grade colonic inflammation caused by fiber deficiency, alleviated colitis, and further prevented colitis-associated colon cancer in mice.