Limitation of the therapeutic potential of DUSP4 through adaptive feedback partially mediated by DUSP5 (IMAGE)
Caption
Figure 1: DUSP4 is a selective dependency in BRAFV600E mutant cancer cell lines.
(A) DUSP4- and BRAF-dependent cell lines are enriched in the BRAFV600E mutant cluster. Gene dependency data of the DUSP paralog family and BRAF originates from the DepMap Consortium database. Columns represent the genes; rows represent the cell lines; dependency Chronos scores are depicted in the tiles, ranging from red (no dependency) to blue (dependency). The dark turquoise annotation bar indicates the BRAFV600E mutant cell lines; the grey annotation bar for BRAF non-V600E mutation carrying cell lines. (B) Proliferation effects after DUSP4 CRISPR depletion in BRAFV600E mutant COLO 201 and HS695T cell lines and in BRAF wild-type A549 cell line measured as GFP signal normalized to day 3 post DUSP4 CRISPR guide transduction. 2 biological replicates are shown. Strong proliferation defects are detected in BRAFV600E mutant cell lines only. BRAFV600E cell lines remain DUSP4 dependent in a BRAF inhibitor resistant setting. (C) Proliferation effect after DUSP4 CRISPR depletion and DUSP4 overexpression or 1 nM trametinib treatment in BRAFV600E mutant COLO 201 and HS695T cell lines. The proliferation effect is measured as GFP signal normalized to day 3 post DUSP4 CRISPR guide transduction. 2 biological replicates are shown. The DUSP4 proliferation effect can be partially rescued by DUSP4 overexpression and completely rescued by MAPK pathway inhibition upstream of DUSP4. (D) Proliferation effect after CRISPR depletion of DUSP paralogs DUSP1, DUSP5 and DUSP6 measured as GFP signal normalized to day 3 post DUSP CRISPR guide transduction. DUSP1, DUSP5 or DUSP6 depletion does not cause a proliferation effect in COLO 201 and HS695T cell lines.
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Copyright: © 2026 Hopfgartner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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