Within the human body, G-protein-coupled receptors (GPCRs) are involved in mediating a plethora of physiological responses. Although their involvement in regulating cancer-associated signaling networks is well known, their actual role in tumor biology is not well understood. It is imperative to determine this for advancing targeted personalized medicine.
During cancer progression, normal human tissue organization is disrupted and cells are maintained outside their normal environment. One such example of this is the activation of cell surface protease-activated receptors (PARs). PARs are a subgroup of GPCRs that form a four-member family. PAR1 and PAR2 play a central role in tumor cell growth in a variety of cancers.
Among the protein modules that drive intermolecular interactions in cellular signaling, the pleckstrin homology (PH) domain is well recognized.
In our most recent work published in the Nature Communications we describe the designs of the PH-PAR complex that are necessary for PAR-driven tumor cell growth, in breast cancer. Deletion of these sites or mutations inserted to these regions potently inhibited tumor development in mouse models. Consequently, these sites may serve as a platform for future targeted therapy.
Our research was conducted through a successful collaboration of Post Doctoral and PhD students, along with the invaluable work of Myriam Maoz from the Sharett Institute of Oncology. Clinical aspects were performed by Prof. Beatrice Uziely, with Prof. Sorina Grisaru-Granovsky completing her PhD in our Laboratory and studying physiological normal invasion process of placenta during pregnancy.
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