When we triggered autophagy response in TNBC, YAP translocated into the nucleus and the expression of YAP target gene ankyrin repeat domain 1 (ANKRD1) increased remarkably.
In conclusion, NPs containing two clinically used drugs concurrently inhibited NF-κB, Wnt, and YAP pathways and exhibited synergic effects on killing TNBC bulk tumor and CSCs.
We also discovered that VEGF-NRP2-YAP/TAZ signaling contributes to the resistance of TNBC cells to cisplatin and that Rad51 rescues the defects in DNA repair upon inhibition of either VEGF-NRP2 or YAP/TAZ.
The expression of total YAP protein in the primary breast cancer tissues was positively associated with the tumor size, especially in triple negative breast cancer (TNBC) subtype (P < 0.05).
These observations were confirmed with cultured tumor fragments prepared from patients with TNBC after treatment with Wnt inhibitor ICG-001 and YAP inhibitor simvastatin.
Our results reveal that YAP1 activation exerts a protective role for TNBC cells in radiotherapy and represents a pharmacological target to enhance the anti-tumor effects of DNA damaging modalities in the treatment of TNBC.