Abstract
Tumorigenesis is correlated with abnormal expression and activity of G protein-coupled receptors (GPCRs) and associated G proteins. Oncogenic mutations in both GPCRs and G proteins (GNAS, GNAQ or GNA11) encoding genes have been identified in a significant number of tumors. Interestingly, uveal melanoma driver mutations in GNAQ/GNA11 were identified for a decade, but their discovery did not lead to mutation-specific drug development, unlike it the case for BRAF mutations in cutaneous melanoma which saw enormous success. Moreover, new immunotherapies strategies such as immune checkpoint inhibitors have given underwhelming results. In this review, we summarize the current knowledge on cancer-associated alterations of GPCRs and G proteins and we focus on the case of uveal melanoma. Finally, we discuss the possibilities that this signaling might represent in regard to novel drug development for cancer prevention and treatment.
Highlights
The G protein-coupled receptor (GPCR) family of proteins comprises more than 800 members and their seven-transmembrane domain structure allows, after binding to their ligands, the activation of heterotrimeric G proteins, which generates second messengers, as well as kinase cascades activation in the cytoplasm of the cells
It is nowadays clearly established that signals transmitted by GPCR/G proteins and downstream targets are involved in the initiation and progression of cancer
We discuss the opportunities offered by altered GPCR/G protein signaling in cancer to develop rational treatment strategies for patients with advanced uveal melanoma
Summary
The G protein-coupled receptor (GPCR) family of proteins comprises more than 800 members and their seven-transmembrane domain structure allows, after binding to their ligands, the activation of heterotrimeric G proteins, which generates second messengers, as well as kinase cascades activation in the cytoplasm of the cells. These signals control gene transcription, cell survival, motility, and growth. We discuss the opportunities offered by altered GPCR/G protein signaling in cancer to develop rational treatment strategies for patients with advanced uveal melanoma
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