Mikel Garcia-Marcos

Focus of Research:

Currently Attending:
University of the Basque Country, Spain

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Metastasis is the cause of more than 90% cancer-related deaths. Despite this frightening numbers, the understanding of the cell biological processes underlying metastasis are poorly understood and the therapeutic strategies to block metastatic progression are very limited. We recently identified a novel signaling mechanism that promotes cancer metastasis in a variety of cancers of epithelial origin (e.g., breast and colorectal). More specifically, we identified that a protein, called GIV, is overexpressed in metastatic tumors, where is works as an activator of trimeric G proteins. From the basic science standpoint, this finding was a breakthrough because trimeric G proteins are traditionally activated by membrane receptors (GPCRs) while GIV is a cytoplasmic protein. Our current research in this area is divided in 3 main lines. One is to identify small molecule inhibitors that disrupt the interaction between GIV and G proteins and to explore their use as anti-metastatic agents. A second line of research is to investigate if other proteins similar to GIV in their molecular function as non-receptor G protein activators are also involved in cancer. In fact, we have already shown that this is the case for DAPLE, another G protein activator of the same class that turns out to regulate Wnt signaling and cancer progression. A third line of research is focused on understanding how GIV and related proteins “rewire” signal transduction to promote cancer metastasis. We are interested in understanding how they regulate the way the tumor microenvironment is sensed by cancer cells and how they interact of with other major signaling mechanism involved in cancer progression. We are actively investigating the interplay between GIV and the enhancement of pro-oncogenic PI3K signaling. Additional information on our research and previous publlications can be found at http://www.bumc.bu.edu/biochemistry/people/faculty/mikel-garcia-marcos/