Tamoxifen Modulates Actin Stress Fibre Dynamics Through c-Src-MLCK Signalling in Breast Cancer Cells.

Emerging evidence suggests that cytoskeletal dynamics are critical in drug resistance and metastasis. The present study investigates the influence of tamoxifen on actin stress fibre organisation in breast cancer cells. We demonstrate that tamoxifen treatment induces significant morphological changes, including increased cell spreading and polarity and enhanced migratory potential in breast cancer cells T47D and ZR-75-1. A loss of organised actin stress fibres and the emergence of lamellipodia and filopodia by tamoxifen treatment indicate its direct role in actin cytoskeleton remodelling, which was further confirmed by western blot analyses of key actin regulators. Upstream tamoxifen activates c-Src kinase, while reducing phosphorylation of myosin light chain (MLC), a key stress fibre regulator that activates myosin II. Further, inhibition of c-Src kinase with PP2 or silencing using siRNA reversed tamoxifen-induced stress fibre loss, confirming c-Src's pivotal role in modulating actin dynamics. These findings highlight a novel mechanism by which tamoxifen influences breast cancer cell actin dynamics and motility.