Supplementary Table 1 from Loss of PKCδ Induces Prostate Cancer Resistance to Paclitaxel through Activation of Wnt/β-Catenin Pathway and Mcl-1 Accumulation

https://doi.org/10.1158/1535-7163.22508229

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posted on 2023-04-03, 15:45 authored by M. Luz Flores, Carolina Castilla, Jessica Gasca, Rafael Medina, Begoña Pérez-Valderrama, Francisco Romero, Miguel A. Japón, Carmen Sáez

<p>Correlation between the expression of PKCÎ', active Î²-catenin, AurKA, phospho-GSK3Î²Ser9 and Mcl-1 with Gleason score and with one another.</p>

Funding

Instituto de Salud Carlos III

Ministerio de Economía y Competitividad

Consejería de Salud

Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía

Consejería de Innovacíon, Ciencia y Empresa, Junta de Andalucía

Nicolás Monardes Program, Consejería de Salud, Junta de Andalucía.

History

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DOI - Is supplement to Loss of PKCδ Induces Prostate Cancer Resistance to Paclitaxel through Activation of Wnt/β-Catenin Pathway and Mcl-1 Accumulation

ARTICLE ABSTRACT

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.