Dickkopf-1 as a critical determinant of malignant bone disease

• Applicants: Dr. Tilmann Rachner; Professorin Dr. Martina Rauner
• Subject Area: Hematology, Oncology
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 179902948

• Final Report Year: 2018

Final Report Abstract

In summary, we were able to show that DKK-1 expression acts as a negative prognostic predictor in ER negative breast cancer and blocking DKK-1 reduces tumor burden in mice. However, the metastastic process is influenced by DKK-1 at different levels and while some aspects are unaltered or inhibited, other aspects like migration are increased by DKK-1 inhibition. Further studies are warranted to elucidate these effects in more detail.

Publications

• P38 regulates the Wnt inhibitor Dickkopf-1 in breast cancer. Biochem Biophys Res Commun. 2015;466:728-32
  Rachner, Tilman D.; Göbel, Andy; Browne, Andrew; Hötzel, Josefa; Rauner, Martina & Hofbauer, Lorenz C.
  
• Potentiated suppression of Dickkopf-1 in breast cancer by combined administration of the mevalonate pathway inhibitors zoledronic acid and statins. Breast Cancer Res Treat. 2015;154:623-31
  Göbel, Andy; Browne, Andrew J.; Thiele, Stefanie; Rauner, Martina; Hofbauer, Lorenz C. & Rachner, Tilman D.
  
• p38 MAPK regulates the Wnt inhibitor Dickkopf-1 in osteotropic prostate cancer cells. Cell Death Dis. 2016;7:e2119
  Browne, A. J.; Göbel, A.; Thiele, S.; Hofbauer, L. C.; Rauner, M. & Rachner, T. D.
  
• Adjuvant tamoxifen but not aromatase inhibitor therapy decreases serum levels of the Wnt inhibitor dickkopf-1 while not affecting sclerostin in breast cancer patients. Breast Cancer Res Treat. 2017;164:737-43
  Göbel, Andy; Kuhlmann, Jan D.; Link, Theresa; Wimberger, Pauline; Browne, Andrew J.; Rauner, Martina; Hofbauer, Lorenz C. & Rachner, Tilman D.
  
• Concurrent antitumor and bone-protective effects of everolimus in osteotropic breast cancer. Breast Cancer Res. 2017;19:92
  Browne, Andrew J.; Kubasch, Marie L.; Göbel, Andy; Hadji, Peyman; Chen, David; Rauner, Martina; Stölzel, Friedrich; Hofbauer, Lorenz C. & Rachner, Tilman D.