Fig. 8: Dual targeting of TGF-β and AURKA pathways enhances the sensitivity to docetaxel-based chemotherapy.

a, b Real-time apoptosis assay of TNBC-M14 and TNBC-M25 3D-MPS treated with 10 nM Docetaxel, 50 nM Galunisertib, and 50 nM Alisertib as single agents and in combination. Apoptotic cells were stained in red with ANNEXIN-V and quantified using the Cell Player System (IncuCyte, BioEssen). Experiments were performed in triplicate (±S.D. and P-value < 0.05). c Representative images of TNBC-M14 and TNBC-M25 3D-MPS treated with 10 nM Docetaxel, 50 nM Galunisertib, and 50 nM Alisertib as single agents and in combination. Apoptotic cells were stained in Red with ANNEXIN-V and quantified in real-time using the Cell Player System (IncuCyte, BioEssen). d TGF-β/AURKA oncogenic axis promotes the enrichment of chemoresistant ALDH^high BTICs: Bulk TNBC cells show a chemosensitive ALDH^low phenotype. Aberrant activation of TGF-β/AURKA/SNAI1 oncogenic axis induces TNBC plasticity resulting in the enrichment of ALDH1^high BTICs with intrinsic resistance to standard chemotherapeutic agents. Dual pharmacologic inhibition of TGF-β and AURKA pathways will impair TNBC plasticity and restore chemosensitivity through the selective targeting of ALDH1^high BTICs.