Research areas and keywords
UKÄ subject classification
- Cancer and Oncology
- GPCR, GPR30, Breast Cancer
We currently explore and exploit a GPCR named GPR30 as a novel receptor target in breast cancer. Initially thought to be a plasma membrane estrogen receptor, we believe that this receptor instead collaborates with the classical estrogen receptor ERα. GPR30 behaves as a tumor-suppressor in ER+ tumors, but some event involving membrane localization and/or overexpression shifts this receptor to directly contribute to cancer progression of ER-, HER2+ tumors, and receptor membrane expression is a strong independent predictor of poor prognosis. GPR30 also associates with a poor response to endocrine treatment with tamoxifen. Using breast cancer cell model systems, patient biopsies, and bioinformatics, we study the underlying reason for the receptor shifting from tumor-suppressive in ER+ tumors to tumor-promoting in ER-, HER2+ tumors. We have found that the receptor physically interacts through its C-terminal end with A-kinase anchoring protein 5 (AKAP5), through which it constitutively sustains increased ERK1/2 signaling and decreased cAMP production, and this interaction appears to define it as a tumor-suppressor. We also study the treatment-predictive value of the receptor, particularly in tamoxifen resistance, and aim to identify novel receptor ligands that can either enhance the tumor-suppressive response or block the tumor-promoting response for therapeutic benefit.
|Effective start/end date||2011/01/01 → …|