Fig. 3: Characterization of drug-naïve and resistant HGSOC cell lines at the molecular and protein levels. | Cell Death & Disease

Fig. 3: Characterization of drug-naïve and resistant HGSOC cell lines at the molecular and protein levels.

From: ROR1-PI3K/AKT signaling drives adaptive resistance to cell cycle blockade in TP53 mutated ovarian cancer

Fig. 3: Characterization of drug-naïve and resistant HGSOC cell lines at the molecular and protein levels.

a UMAP plots showing the distribution of drug-naïve and long-term resistant cells for each HGSOC cell line. Colors denote cell line and treatment condition. b Bar charts showing the proportion of cells (%) in each cell cycle phase across cell lines and treatment conditions. c Heatmap illustrating the scaled signaling pathway activity scores of PROGENy pathways in PTX lt-res and ADA lt-res cell lines and parental cells. Red color indicates higher pathway activity, and blue color indicates lower pathway activity. d Heatmaps of gene modules for each cell line. Letters A-D indicate the gene modules identified within each cell line. Columns represent signatures (gene sets derived from cell clusters), and rows represent the genes within each module. Color indicates z-scored expression of module genes across signatures (capped at ± 3). The stacked bars below each heatmap show the percentage of cells from each condition present in each signature. e Dot plot showing shared significantly enriched pathways among the gene modules identified in panel d (JHOS2 ADA module A, Kuramochi ADA modules A, B, C, Ovsaho ADA module A, JHOS2 PTX modules B, C and COV318 PTX modules C, D). Dot size represents the gene ratio, and dot color corresponds to the adjusted p-value. f Immunoblot analysis for signaling pathways of interest in drug-naïve and lt-res models. β-actin was used as loading control. Below, a schematic representation of the two PI3K/AKT-regulated drug resistance mechanisms, with background colors matching the lt-res models where the mechanisms were active. Left (PI3K/AKT OFF): Nuclear FOXO3 represses MYC, activates DNA Damage Response (DDR, ATR/CHK1), and together with active WEE1 stalls cells in G2, leading to replication stress responses. Right (PI3K/AKT ON): AKT phosphorylates FOXO3 (pFOXO3) causing its cytoplasmic retention, induction of FOXM1/MYC, reduced WEE1 function, and RTK upregulation (e.g., ROR1), enabling mitotic escape and survival.

Back to article page