Fig 1: PCDH9 as a candidate effector linked to APOBEC-associated pro-tumorigenic signaling in CRC. (a) Relative deaminase activity measured in control, OE-APOBEC3B Mut, and OE-APOBEC3B CRC cells. (b) Volcano plot showing differentially expressed genes between OE-A3B and OE-A3B Mut groups. (c) Network visualization of pathway enrichment results highlighting significant involvement of Hippo, Wnt/β-catenin, and TGF-β signaling pathways. (d) Bar plot comparing activity scores of Hippo, Wnt/β-catenin, and TGF-β pathways between OE-A3B Mut and OE-A3B groups. (e) ELISA quantification of BMP6 (left) and WNT7B (right) secretion in the indicated cell groups. (f) Correlation heatmap illustrating associations between the 22 AAS signature genes and the APOBEC AAS. (g) Polar bar plot showing correlation coefficients of six top AAS-associated genes. (h) Schematic diagram showing the proposed working model in which APOBEC-associated alteration of PCDH9 may contribute to Hippo, Wnt/β-catenin, and TGF-β signaling changes. (i) Schematic representation of TCW motif mutations identified in PCDH9 and their predicted structural impact. (j) Predicted 3-D structures of APOBEC-associated mutant PCDH9 protein (left) and wild-type (right), suggesting a potential conformational impact of the mutation. These structural predictions were used to generate mechanistic hypotheses and do not constitute direct experimental evidence of altered protein stability or function. (k) Western blot validation of APOBEC3B and PCDH9 overexpression in HCT116 and LoVo cells. (l) Western blot analysis of Hippo pathway components (MST1/2, p-MST1/2, LATS1, p-LATS1, YAP, p-YAP) under indicated conditions. (m) Western blot analysis of Wnt/β-catenin pathway proteins (GSK-3β, Axin, β-catenin, S100A4, c-MYC, ANGPT2). (n) Western blot analysis of TGF-β pathway components (TGFβR1, TGFβR2, SMAD2/3, p-SMAD2/3, SERPINE1). * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.