FIGURE

Fig. 7

ID

ZDB-FIG-200625-7

Publication

Das et al., 2020 - AXL and CAV-1 play a role for MTH1 inhibitor TH1579 sensitivity in cutaneous malignant melanoma

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Fig. 7

Schematic illustration how TH1579 downregulates AXL and CAV-1 expression and induces ROS, leading to DNA damage and cell death.

a In BRAF mutant CMM, TH1579 treatment inhibits MTH1, elevates ROS, causes a mitotic arrest, DNA damage and reduced AKT signaling. Combining BRAF inhibitor vemurafenib and TH1579 results in additive/synergistic responses by affecting several pathways leading to apoptosis and cell death. b BRAF inhibitor resistant CMM have upregulated levels of AXL and CAV-1, resulting in overactivated MAPK signaling overriding the effect of BRAF inhibitor. In addition to the effects of TH1579 observed in BRAF-mutated CMM, TH1579 downregulates AXL and CAV-1 levels, resulting in improved efficacy of BRAF inhibitor treatment. cNRAS mutated CMM has upregulated AXL compared with BRAF mutated and WT CMM and TH1579 treatment reduces the level of AXL, hinder AKT signaling, induces ROS, causes DNA damage, mitotic arrest and cancer cell death. d By overexpressing AXL in WT and BRAF-mutated CMM, increased ROS levels and improved efficacy following TH1579 treatment was observed.

Expression Data

Expression Detail

Antibody Labeling

Phenotype Data

Phenotype Detail

Acknowledgments

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