Identification of Mechanisms of ZEB1 Regulation by PKC Signaling Pathway in Breast Cancer Progression
María Candelaria Llorens de los Ríos
University of Pennsylvania
Characterizing genes that regulate the metastatic ability of breast cancers may identify novel biomarkers to help clinicians perform novel treatments, and may offer new targets for therapy. To acquire the invasive abilities, cancer cells must undergo phenotypic changes termed epithelial-mesenchymal transition(EMT). ZEB1 is strongly involved in EMT in cancer. The home lab identified phosphosites in ZEB1 phosphorylated by PKC which results in changes in ZEB1 transcriptional activity in normal cells. However, we have yet to examine closely the relationship between PKC and ZEB1 in breast cancer progression and metastasis. In 2015 the home and host laboratories started collaboration with promising data to define a new mechanism of ZEB1 regulation in EMT by PKC in breast cancer cells. I propose to study in detail the effect of PKCon EMT and cancer progression through ZEB1 regulation. The Aims are: a) to examine whether ZEB1 regulation by PKC takes place at either the transcriptional or post transcriptional level; b) to study the functional relevance of interaction;c) to identify phosphorylation sites of ZEB1 which are PKC substrates by mass spectrometry.