Fig. 7: Effect of HER2 dimerization domain mutations (DDMs) on cell invasion and migration properties.

A Graph showing collective migratory capabilities of wild-type HER2 (H2-WT) or DDM expressing ZR-75-1 cells. G309A, S310Y, and P523S mutant expressing cells exhibit nearly complete wound closure within 48 h, indicating enhanced migratory potential. The graph is representative of 3 biological replicates. These cells remain unresponsive to neratinib treatment, showing no change in wound closure capabilities. B Representative photomicrographs of CalceinAM stained H2-WT or DDM expressing ZR-75-1 cells showing matrigel invasive capabilities in absence or presence of p-AKT and p-ERK inhibitors. The graph is representative of 3 biological replicates (C) Heatmap showing the quantified total cell fluorescence/field of results as in (B). Corrected total cell fluorescence values were compared between untreated and treated conditions, ns-non-significant; **P < 0.01; ***P < 0.001 ****P < 0.0001. D Annexin V/PI-stained flow cytometry results showing H2-WT or the DDMs expressing cells before and after tucatinib treatment. E Representative photomicrographs showing matrigel invasive capabilities of H2-WT or the DDM expressing cells with or without tucatinib treatment. F Z-Score heatmap of H2-WT, S310Y and P523S mutant expressing cells against newer regimens of HER2 targeted therapy.