Tandem Andy Goebel & Tilman Rachner (Alumni)
Signalling pathways control cell and tissue growth during development and regeneration. One of these critical pathways is Wnt signalling, which is particularly involved in bone remodelling and skeletal homeostasis. Mutations and hyperactivation of Wnt signalling proteins and regulators are implicated in tumorigenesis. Dickkopf-1 (DKK-1) is a secreted, negative regulator of WNT signalling and blocks the differentiation of bone-building osteoblasts. High levels of DKK-1 are associated with osteolytic bone metastasis in multiple myeloma and breast cancer. However, additional effects of DKK-1 in cancer, apart from its role in bone biology, have been identified. These include the mediation of stress resistance mechanisms and the recruitment of tumor-promoting myeloid-derived suppressor cells into the tumor microenvironment.
Current research of the Göbel/Rachner team explores the potential of DKK-1 as a target in personalized and precision therapy of human cancers. Preliminary experiments in human cancer cell lines demonstrated that DKK-1 regulates the androgen receptor (AR) in prostate cancer cells. Moreover, breast cancer cells lacking DKK-1 show an increased dependence on glutamine. As DKK-1 can be blocked genetically by CRISPR/Cas9 technology and small-interfering RNAs or pharmacologically by neutralizing antibodies, its potential as a target for personalized cancer therapy will be explored.
- Identify breast cancer patient subpopulations that would mostly benefit from an anti-DKK-1 and glutamine metabolism-targeted therapy
- Elucidate the potential of DKK-1 as a valid predictor of endocrine resistance for individualized risk stratification in patients with prostate cancer
- Assess the potential of the mevalonate pathway as a therapeutic target in human malignancies
- Identification of novel biomarkers in osteotropic malignancies
Lab members
Selected publications
Andy Göbel, Stefania Dell’Endice, Nikolai Jaschke, Sophie Pählig , Amna Shahid , Lorenz C. Hofbauer and Tilman D. Rachner The Role of Inflammation in Breast and Prostate Cancer Metastasis to Bone International Journal of Molecular Science. 2021, 22(10), 5078
Göbel A, Rauner M, Hofbauer LC, Rachner TD. C Cholesterol and beyond - The role of the mevalonate pathway in cancer biology. Biochim. Biophys. Acta - Rev. Cancer. 2020; 1873:188351.
Rachner TD, Göbel A, Hoffmann O, Erdmann K, Kasimir-Bauer S, Breining D, Kimmig R, Hofbauer LC, Bittner A-K. . High serum levels of periostin are associated with a poor survival in breast cancer. Breast Cancer Res. Treat. 2020; 180:515–24.
Rachner TD, Kasimir-Bauer S, Göbel A, Erdmann K, Hoffmann O, Browne AJ, Wimberger P, Rauner M, Hofbauer LC, Kimmig R, Bittner AK. Prognostic value of RANKL/OPG serum levels and disseminated tumor cells in non-metastatic breast cancer. Clin Cancer Res 2019; 25:1369-1378.
Rachner TD, Göbel A, Thiele S, Rauner M, Benad-Mehner P, Hadji P, Bauer T, Muders MH, Baretton GB, Jakob F, Ebert R, Bornhäuser M, Schem C, Hofbauer LC. Dickkopf-1 is regulated by the mevalonate pathway in breast cancer. Breast Cancer Res. 2014 16:R20.
Links
Open postions
We are looking for a motivated technician (MTA, BTA, CTA) to complement our team as soon as possible. Check out the job offer, we are happy to receive your application!
Contact
© Marc Eisele
Tandemlab Goebel/Rachner
Besuchsadresse:
Division of Endocrinology, Diabetes, and Bone Diseases Dresden
Haus19/5th floor, 5.128
Fetscherstraße 74
01307 Dresden
Postadresse:
Technische Universität Dresden Division of Endocrinology, Diabetes, and Bone Diseases Dresden Fetscherstrasse 74
01307 Dresden