BRAF, A gatekeeper controlling endothelial permeability

Abstract

The RAF/MEK/ERK signal transduction pathway is commonly deregulated in cancer and is activated by various stimuli regulating a variety of cell responses. In wild‐type endothelial cells, upon permeability stimuli, ROKα, RAF1, BRAF, and RAP1 become activated, inducing a cascade of reactions resulting in F‐actin remodeling and increased cell permeability. Here, Dorard et al. showed that BRAF ablated cells had more RAF1/ROKα dimerization and relocalization to VE‐cadherin occurred, ultimately leading to less F‐actin content and reduced vessel permeability.

BRAFV600E mutant colorectal cancer cells mediate local immunosuppressive microenvironment through exosomal long noncoding RNAs

“…BRAF V600E mutation can promote the expression of matrix metalloproteinase-2 and VEGF-A in malignant melanoma cells, mediate angiogenesis, and enhance the invasiveness of tumor cells. However, BRAF gene deletion leads to a lack of VEGF-A, inhibiting angiogenesis and minimizing the permeability between endothelial cells[ 33 ]. Additional research has also proposed that BRAF V600E mutant thyroid cancer cells can promote angiogenesis and lymphoangiogenesis by releasing VEGF-A and VEGF-C into the TME.…”