RT Journal Article
T1 Loss of PKCδ Induces Prostate Cancer Resistance to Paclitaxel through Activation of Wnt/β-Catenin Pathway and Mcl-1 Accumulation.
A1 Flores, M Luz
A1 Castilla, Carolina
A1 Gasca, Jessica
A1 Medina, Rafael
A1 Perez-Valderrama, Begoña
A1 Romero, Francisco
A1 Japon, Miguel A
A1 Saez, Carmen
K1 Antineoplastic Agents, Phytogenic
K1 Cell Cycle Checkpoints
K1 Gene Silencing
K1 Models, Biological
K1 Protein Kinase C-delta
AB Prostate cancer is the leading cause of cancer-related death among men in developed countries. Although castration therapy is initially effective, prostate cancers progress to hormone-refractory disease and in this case taxane-based chemotherapy is widely used. Castration-resistant prostate cancer cells often develop resistance to chemotherapy agents and the search for new therapeutic strategies is necessary. In this article, we demonstrate that PKCδ silencing favors mitotic arrest after paclitaxel treatment in PC3 and LNCaP cells; however, this is associated with resistance to paclitaxel-induced apoptosis. In prostate cancer cells, PKCδ seems to exert a proapoptotic role, acting as a negative regulator of the canonical Wnt/β-catenin pathway. PKCδ silencing induces activation of Wnt/β-catenin pathway and the expression of its target genes, including Aurora kinase A, which is involved in activation of Akt and both factors play a key role in GSK3β inactivation and consequently in the stabilization of β-catenin and antiapoptotic protein Mcl-1. We also show that combined treatments with paclitaxel and Wnt/β-catenin or Akt inhibitors improve the apoptotic response to paclitaxel, even in the absence of PKCδ. Finally, we observe that high Gleason score prostate tumors lose PKCδ expression and this correlates with higher activation of β-catenin, inactivation of GSK3β, and higher levels of Aurora kinase A and Mcl-1 proteins. These findings suggest that targeting Wnt/β-catenin or Akt pathways may increase the efficacy of taxane chemotherapy in advanced human prostate cancers that have lost PKCδ expression. Mol Cancer Ther; 15(7); 1713-25. ©2016 AACR.
PB American Association for Cancer Research
YR 2016
FD 2016
LK http://hdl.handle.net/10668/10102
UL http://hdl.handle.net/10668/10102
LA en
NO Flores ML, Castilla C, Gasca J, Medina R, Pérez-Valderrama B, Romero F, et al.  Loss of PKCδ Induces Prostate Cancer Resistance to Paclitaxel through Activation of Wnt/β-Catenin Pathway and Mcl-1 Accumulation. Mol Cancer Ther. 2016 Jul;15(7):1713-25.
DS RISalud
RD Jul 31, 2025