A5075499003- Melanoma and MAPK Pathways
- Cytokine Signaling Pathways and Interactions
- Computational Drug Discovery Methods
- NF-κB Signaling Pathways
- Protein Kinase Regulation and GTPase Signaling
- Cancer Mechanisms and Therapy
- interferon and immune responses
- Cell Adhesion Molecules Research
- vaccines and immunoinformatics approaches
Memorial Sloan Kettering Cancer Center
2018-2025
Abstract BRAFV600E mutations occur in 46% of melanomas and drive high levels ERK activity ERK-dependent proliferation. However, is insufficient to melanoma genetically engineered mouse models, 82% human benign nevi harbor mutations. We found that inhibited mesenchymal migration by causing feedback inhibition RAC1 activity. pathway induced activation restored invasion. In cells with BRAFV600E, mutant or PTEN inactivation cell motility. Together, these lesions occurred 26% Thus, although...
RAF protein kinases are effectors of the GTP-bound form small guanosine triphosphatase RAS and function by phosphorylating MEK. We showed here that expression ARAF activated in a kinase-independent manner. Binding to displaced GTPase-activating NF1 antagonized NF1-mediated inhibition RAS. This reduced ERK-dependent increased RAS-GTP. By this mechanism, regulated duration consequences RTK-induced activation supported output RTK-dependent tumor cells. In human lung cancers with EGFR mutation,...
Abstract BRAF V600E mutation occurs in 46% of melanomas and drives high levels ERK activity ERK-dependent proliferation. However, is insufficient to drive melanoma GEMM models, 82% human benign nevi harbor mutations. We show here that inhibits mesenchymal migration by causing feedback inhibition RAC1 activity. pathway induces activation restores invasion. In cells with , mutant RAC1, overexpression PREX1, PREX2, or PTEN inactivation restore cell motility. Together, these lesions occur 48%...