PKCa Modulates Epithelial-to-Mesenchymal Transition and Invasiveness of Breast Cancer Cells through ZEB1

LLORENS, MARÍA CANDELARIA; ROSSI, FABIANA ALEJANDRA*; GARCÍA, IRIS ALEJANDRA*; COOKE, MARIANA; ABBA, MARTIN C.; LOPEZ HABER, CYNTHIA; BARRIO-REAL, LAURA ; VAGLIENTI, MARÍA VICTORIA; ROSSI, MARIO ; BOCCO, JOSÉ LUIS; KAZANIETZ, MARCELO G.#; SORIA, GASTÓN#; LOS AUTORES * Y # CONTRIBUYERON DE IGUAL MANERA

Frontiers in Oncology

Frontiers

Lugar: Lausanne; Año: 2019

EB1 is a master regulator of the Epithelial-to-Mesenchymal Transition (EMT) program. While extensive evidence confirmed the importance of ZEB1 as an EMT transcription factor that promotes tumor invasiveness and metastasis, little is known about its regulation. In this work, we screened for potential regulatory links between ZEB1 and multiple cellular kinases. Exploratory in silico analysis aided by phospho-substrate antibodies and ZEB1 deletion mutants led us to identify several potential phospho-sites for the family of PKC kinases in the N-terminus of ZEB1. The analysis of breast cancer cell lines panels with different degrees of aggressiveness, together with the evaluation of a battery of kinase inhibitors, allowed us to expose a robust correlation between ZEB1 and PKCα both at mRNA and protein levels. Subsequent validation experiments using siRNAs against PKCα revealed that its knockdown leads to a concomitant decrease in ZEB1 levels, while ZEB1 knockdown had no impact on