NEDD4 (NEDD4 E3 Ubiquitin Protein Ligase)

Our data further demonstrated that pharmacological or genetic inhibition of c-Myc effectively reversed the resistance phenotype mediated by HDAC5 loss, suggesting a therapeutic strategy centered on "KRAS-MYC dual-node blockade." Furthermore, the expression levels of HDAC5 and the acetylation status of c-Myc may serve as potential biomarkers for predicting the therapeutic response to MRTX1133. These findings provide insights into overcoming resistance to KRASG12D inhibitors and offer potential biomarkers and combinatorial therapeutic strategies for precision treatment of PDAC.

N4BP2 promoted genome rearrangements (including chromothripsis), formation of extrachromosomal DNA (ecDNA) in drug-induced gene amplification, tumorigenesis, and tumor cell proliferation in an induced model of human high-grade glioma. Analysis of more than 10,000 human cancer genomes revealed elevated N4BP2 expression to be predictive of chromothripsis and copy number amplifications, including ecDNA.

In conclusion, this study further identifies NDFIP1 as a novel target of PF-429242, partially responsible for its induction of autophagy in HCC cells. These findings offer a promising therapeutic avenue for treating HCC.

Increased matrix stiffness significantly promoted glycolysis in HCC cells via upregulating PFKFB3 expression. High stiffness stimulation suppressed PFKFB3 ubiquitination by downregulating E3 ubiquitin ligase NEDD4 expression. PFKFB3 participated in DNA damage repair by translocating into nuclear and interacting with Ku70, which strengthened by matrix stiffness.

miR-155-5p emerges as a promising diagnostic marker and therapeutic candidate, suggesting the feasibility of miRNA-based interventions in BC treatment. This study highlights the pivotal role of integrative omics technologies in uncovering cancer-related regulatory networks.

Furthermore, a small-molecule inhibitor of NEDD4, XMU-MP-10, exhibits significant in vivo efficacy in inhibiting TNBC tumor growth by enhancing CD8+ T cell infiltration in mouse models. Collectively, our findings suggest that the genetic depletion or pharmacological inhibition of NEDD4 enhances antitumor immune responses via the β-TrCP/YAP/ECM cascades, offering a promising therapeutic strategy for TNBC treatment.

TCEB2 upregulation promoted TNBC-induced M2 macrophage polarization to accelerate TNBC development by mediating Slit2 K63-ubiquitination degradation through interacting with NEDD4.

Taken together, N4BP3 promotes ovarian cancer progression and PTX resistance by activating the Wnt/β-catenin signaling through interaction with XPO1. N4BP3 may serve as a potential therapeutic target for the treatment of ovarian cancer.

These findings highlight the crucial role of the BMI1/FGFR1 axis in OSI resistance and provide a rational basis for the future clinical application of the biguanide, SMK-010, in combination with OSI.

Based on the signature of ubiquitination-related genes (URGs), differentially expressed genes between cisplatin-resistant and cisplatin-sensitive SCLC cell lines were identified using the Genomics of Drug Sensitivity in Cancer (GDSC) database...Cell viability, wound healing and transwell invasion assays demonstrated that NEDD4 promoted the proliferation, chemoresistance and invasion of SCLC cells. These results suggest that NEDD4 is a biomarker of a poor prognosis for SCLC, and that it promotes AKT activation, SCLC progression and chemoresistance.

Moreover, CRC patients with low STK25 expression are more responsive to immune checkpoint blockade (ICB) therapy compared to those with high STK25 levels. Taken together, the findings reveal a critical role of STK25 for regulating PD-L1 protein stability in tumor immune evasion, and suggest that targeting STK25 may provide a potential approach to increase sensitivity to the ICB treatment in patients with CRC.

Additionally, when combining positive ß-catenin expression and sequencing results, the aberrant/mutant CTNNB1 gene was shown in three tumors (75% of analyzed cases) in this IPM series. The present data provides additional support/adjunct to establish the rare diagnosis of intranodal palisaded myofibroblastomas with amianthoid fibers by molecular testing in diagnostically challenging cases.