NGEF (Neuronal Guanine Nucleotide Exchange Factor)

This suggests that Ephexin1 could serve as a synthetic lethality target for mTORC1-targeting therapeutics in cancer treatment. Our findings provide mechanistic insights into the role of Ephexin1 in cancer pathogenesis and highlight its potential as a therapeutic target for improving current cancer treatment strategies.

These studies confirmed that BRAFV600E regulates NGEF expression via the ERK/AP1 pathway. These findings suggest that NGEF enhances the invasive and migratory abilities of BRAFV600E-mutant thyroid cancer cells through BRAFV600E/ERK/AP1 upregulation and may serve as a potential therapeutic target for BRAFV600E-mutant thyroid cancer cells.

NGEF facilitates the infiltration of nerve and the growth of cancer cells in lung adenocarcinoma through the Ephrin-A3/EphA2 pathway, suggesting that NGEF is a promising target for disrupting interactions between nerves and tumors. Biomaterials that focus on NGEF are anticipated to be a potential treatment option for lung cancer.

Importantly, our findings also suggest that targeting Ephexin1 may increase the efficacy of Wnt/β-catenin pathway inhibitors in CRC treatment. These findings highlight the potential of targeting Ephexin1 as a strategy for developing effective treatments for CRC, suggesting a novel and promising approach to therapy aimed at inhibiting cancer progression.

Furthermore, Ephexin4 knockdown exacerbated vincristine-induced chromosome misalignment, which was prevented by re-expressing the wild-type but not S41A Ephexin4...Our results suggest that Ephexin4 undergoes phosphorylation at Ser41 in cell division, and the phosphorylation is required for chromosome alignment through RhoG activation. Combined with mitosis-targeting agents, inhibition of Ephexin4 phosphorylation may represent a novel strategy for cancer chemotherapy.

NGEF expression is upregulated in LUAD and is significantly associated with tumor stages, OS probability, immune infiltration, immunotherapy response, and chemotherapy response. NGEF may be a potential diagnostic and prognostic biomarker and therapeutic target in LUAD.

The signaling landscape that accompanies Ephexin3 in various cancer types included the tyrosine kinase receptor MET and the tyrosine phosphatase receptor PTPRF, the serine/threonine kinases MARK2 and PAK6, the Rho GTPases RHOD, RHOF and RAC1, and the cytoskeletal regulator DIAHP1. Our findings set the basis to further explore the role of Ephexin3/ARHGEF5 as an essential effector and signaling hub in cancer cell migration.