Figure 8: The role of the TEADs in drug resistance of the invasive melanoma state.
From: Decoding the regulatory landscape of melanoma reveals TEADS as regulators of the invasive cell state
(a) Analysis of CCLE data (n=39) shows a significant difference of IC50 values for both the BRAF and MEK inhibitors (PXL4032 and AZD6244), where cell lines with a high TEAD signature (top 25%) are more resistant compared with the other cell lines. (b) IC50 curves showing a strong resistance of invasive cultures (MM029, MM047 and MM099, orange shades) for both BRAF and MEK inhibitors (PLX4032 and Pimasertib) compared with two proliferative cultures (MM074 and MM034, blue shades) both at 48 and 72 h of exposure. MM047 data were not incorporated in BRAF-related plots since this culture does not harbour the V600E BRAF mutation. (c) IC50 shifts indicating a sensitization of the invasive lines for the MEK inhibitor measured at 48 and 72 h of treatment when treated with siRNAs against all four TEADs. All error bars represent s.e.m. and are the result of at least three biological replicates. P-values were determined using Student’s t-test.
