MAP2K1 (Mitogen-activated protein kinase kinase 1)

We also showed that a 16-residue-long arrestin-3-derived peptide binds ZAK and fulfills the scaffolding function of full-length arrestin-3, sensitizing cells to death induced by chemotherapy drugs. These findings demonstrate that arrestin-3 is a versatile facilitator of stress signaling and suggest that functional peptide mimics can be used therapeutically to facilitate drug-induced death of cancer cells.

Furthermore, RA synergized with anti-PD-1 therapy and enhanced the efficacy of adoptively transferred OT-I T cells in colorectal tumor-bearing hosts. Collectively, our findings reveal RA as a novel immunomodulatory agent that boosts CD8⁺ T cell responses via MEK1-mediated TCR signaling enhancement, providing a promising strategy for drug repurposing in cancer immunotherapy.

Genetic loss of KLF4 or AXL depletion reduced melanoma cell migration and invasion, suggesting a key role of KLF4 in the regulation of invasiveness. Our study describes a novel ERK5/KLF4/AXL signaling axis that drives MEKi resistance and metastatic potential in NRAS-mutant melanoma and highlights this axis as a potential target to improve MAPK-directed and potentially immune therapies.

PRMT1 inhibition decreased the asymmetric dimethylarginine of MAST1 at R806 and downregulated the activation of the MAPK pathway by affecting the phosphorylation of MEK1 and ERK1/2 in CLL cells. In summary, our results indicated that PRMT1 promoted CLL tumorigenesis via MAST1-mediated regulation of MEK1 signaling and highlighted the potential of C7280948 as a novel therapeutic agent for CLL treatment.

In conclusion, this study demonstrates that central proteins in the RAS signaling pathway exhibit functional diversity that underpins their importance in cancer progression. These findings provide a reproducible network-based workflow for identifying pathway-relevant molecular candidates and contribute to the development of more precise, pathway-oriented cancer therapies.

Our study suggests that 14-3-3β modulates the phosphorylated alterations of the cancer-related proteome. Unveiling the role of the 14-3-3β/Hsp90B pathway in GC CDDP resistance implies it could serve as a potential therapeutic target for treating CDDP-resistant GC patients.

When combined with EGFR inhibitors (osimertinib and gefitinib) in PC9 cells, the mimics showed a higher rate of growth inhibition compared with the controls and reduced IC50 values. Similarly, conmiR-15/107 enhanced growth inhibition by the KRAS inhibitors sotorasib and adagrasib in H358 cells...Long-term assays showed that the mimics reduced the survival and delayed the proliferation of DTPs in osimertinib-treated PC9 cells as well as sotorasib-treated H358 cells. These findings support conmiR-15/107 as a potential adjunct to targeted therapy, capable of enhancing treatment efficacy and delaying resistance in lung adenocarcinoma.

SM-23 enhances MEK/ERK pathway inhibition through improved kinase binding affinity and demonstrates potent antiproliferative activity in colorectal cancer cells. These findings identify SM-23 as a promising MEK/ERK-targeted candidate for further therapeutic development.

MKK6 directly phosphorylated BCL2L13 at serine 426, enhancing the interaction between BCL2L13 and LC3B, which, in turn, promoted mitophagy, inhibited oxidative phosphorylation (OXPHOS), and prevented tumor growth. Our studies not only revealed that MKK6-BCL2L13 phosphorylation at the interorganellar site can affect mitochondrial quality in tumorigenicity but also might provide a potential therapeutic strategy for LUAD treatment.

Our findings elucidate multiple mechanisms by which CGs may exert anti-LSC activity, which could be crucial for the design of novel therapeutic strategies for AML. The proposed in silico framework is broadly applicable and may accelerate drug repurposing in AML and other cancers.

Only one patient died 16 months after surgery due to an unrelated traffic accident.

The presence of MS appeared to correlate with worse clinical outcomes, as 67% of patients with MS died, compared to none without. Our findings expand the recognized molecular diversity of MBNs and provide insights into their biological behaviors, underscoring the clinical significance of identifying potential prognostic factors.