SPEAKER: Marcelo G. Kazanietz (University of Pennsylvania)
TITLE: Unraveling Oncogenic and Metastatic Signaling Networks: the Protein Kinase and Small GTPase Interplay
DATE: Wednesday, April 12, 12 p.m.
VENUE: IBioBA´s seminar room. Godoy Cruz 2390, C1425FQD, Buenos Aires, Argentina.
Abstract
The genesis and progression of cancer involves a series of genetic and epigenetic cellular alterations leading to aberrant mitogenic and survival signaling, as well as to the acquisition of invasive traits that promote metastasis to distant sites. Deregulated production and/or degradation of lipid second messengers such as diacylglycerol (DAG) and phosphatidylinositol-3,4,5-triphosphate (PIP3), or functional anomalies in the expression/activation status of their effectors, represent major contributing factors to malignant cell transformation and the acquisition of metastatic traits. Our laboratory identified fundamental contributions for lipid effector kinases and small G-protein regulators in prostate, breast, lung and other cancers. Protein Kinase C (PKC) isozymes and Rac-Guanine-nucleotide Exchange Factors (Rac-GEFs) were found to play key roles in the control of tumorigenic signaling pathways and transcriptional networks, thus contributing to specific steps of cancer initiation, progression and metastasis. By means of genetically-engineered mouse models, we established functional associations of PKCs with oncogenes (such as KRAS) and tumor suppressors (such as PTEN). Ongoing efforts are directed to dissect the molecular basis of these signal transduction aberrations and the relationship of these pathways with the tumor microenvironment (TME), with the ultimate goal of paving the way to novel antitumor therapeutic approaches.