Advanced Medical Scientist Programm 2024

Thema: ETAR in ovarian carcinoma: Modulation of signaling activity by kinases and phosphatases

Zusammenfassung:
The G protein coupled receptor (GPCR) endothelin receptor type A (ETAR) was found to be an important player in many different cancer types, among them ovarian carcinoma. Specific GPCR kinases (GRKs) phosphorylate the receptor and initiate its
desensitization via β-arrestins. One of the GRKs, GRK5 was reported to be significantly downregulated in ovarian cancer patient samples. In initial studies, we identified GRK5 as the most important GRK in regulating β-arrestin recruitment and ETAR trafficking. Therefore, we will investigate the influence of GRK5 on the ETAR signaling and the malignancy of ovarian carcinoma. The dephosphorylation by phosphatases (PPs) is in general understudied in the GPCR field, despite its crucial
role in resensitization of the receptor. We plan to identify the phosphatases acting on the ETAR and will create KO cell lines to further study their part in mediating the malignant potential of the ovarian carcinoma cell line A2780. The molecular insights
that will be gained in this project will open the possibility to identify novel treatment strategies for this hard to treat cancer type.