Figure 1 from SM08502-Mediated β-Catenin Repression Synergizes with Olaparib to Inhibit Tumor Progression
Year: 2025
Type: other
Abstract: WNT signaling and TCF activity promote PARPi resistance and are sensitive to SM08502. A, PARPi-sensitive (-S) PEO1 (BRCA2-mutated) and (B) UWB1.289 (BRCA1-mutated) cell lines were transduced with WNT3A (-Wnt3a) or developed to be olaparib-resistant (-OR). Cells were treated with increasing doses of olaparib, and cell survival was measured via colony formation. C, PEO1 (-S, -Wnt3a, and -OR) and (D) UWB1.289 (-S, -Wnt3a, and -OR) cells treated with increasing doses of talozoparib. E, PEO1 (-S, -Wnt3a, and -OR) and (F) UWB1.289 (-S, -Wnt3a, and -OR) cells were treated with increasing doses of rucaparib. G, PEO1 (-S, -Wnt3a, and -OR) and (H) UWB1.289 (-S, -Wnt3a, and -OR) cells were treated with increasing doses of a novel pan-CLK/DYRK inhibitor—SM08502. I, PEO1-OR and (J) UWB1.289-OR cells were treated with increasing doses of SM08502, and TCF transcriptional activity was measured via TOP/FOP-FLASH assay. K, PEO1-Wnt3a and (L) UWB1.289-Wnt3a cells were treated with increasing doses of SM08502, and TCF transcriptional activity was measured via TOP/FOP-FLASH assay. M, Patients with HGSC treated with PARPis stratified based on the median of TCF7L1 mRNA expression. N, Same as (M) but with median TCF7L2 mRNA expression. Error bars, SEM. Statistical test, nonlinear regression, ANOVA with Tukey multiple comparison test, Kaplan–Meier with log-rank. IC50 concentration is shown as an inset for each graph. CI, confidence interval.
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4416979532
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