A switch in RND3-RHOA signaling is critical for melanoma cell invasion following mutant-BRAF inhibition.

ABSTRACT:

Background

The initial use of BRAF targeted therapeutics in clinical trials has demonstrated encouraging responses in melanoma patients, although a rise in drug-resistant cells capable of advancing malignant disease has been described. The current study uses BRAFV600E expressing WM793 melanoma cells to derive data aimed at investigating the molecular determinant of cell invasion following treatment with clinical BRAF inhibitors.

Findings

Small-molecule inhibitors targeting BRAF reduced MEK1/2-ERK1/2 pathway activation and cell survival; yet, viable cell subpopulations persisted. The residual cells exhibited an elongated cell shape, prominent actin stress fibers and retained the ability to invade 3-D dermal-like microenvironments. BRAF inhibitor treatments were associated wit

SUBMITTER: Klein RM 

PROVIDER: S-EPMC3180434 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature