The Garcia-Marcos lab, in collaboration with members of the Department of Chemistry at Boston University and the CSIC-CIB in Spain, have published in Proceeding of the National Academy of Sciences (PNAS) the discovery of a chemical compound that specifically blocks an aberrant mechanism of signaling in cancer cells that drives invasion and metastasis. The publication can be found here: https://www.pnas.org/doi/10.1073/pnas.2213140120
Human diseases frequently arise from defects in the mechanisms by which external cues are sensed and relayed to the interior of the cell. The proteins most widely targeted by existing therapeutic agents belong to a large family of cell surface receptors named G-protein-coupled receptors (GPCRs), which relay external cues by activating G-proteins in the interior of cells. Here, we report the surprising discovery of a synthetic small molecule that selectively targets G-proteins without compromising their ability to relay signals from GPCRs. Instead, this small molecule disrupts an atypical, GPCR-independent mechanism of G-protein signaling involved in cancer. This work reveals an alternative paradigm in targeting components of a signaling machinery with broad relevance in cellular communication in health and disease.