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 TD, Göbel A, Browne A, Hötzel J, Rauner M, Hofbauer LC
  (See online at https://doi.org/10.1016/j.bbrc.2015.09.101)
• 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 A, Browne AJ, Thiele S, Rauner M, Hofbauer LC, Rachner TD
  (See online at https://doi.org/10.1007/s10549-015-3624-8)
• p38 MAPK regulates the Wnt inhibitor Dickkopf-1 in osteotropic prostate cancer cells. Cell Death Dis. 2016;7:e2119
  Browne AJ, Göbel A, Thiele S, Hofbauer LC, Rauner M, Rachner TD
  (See online at https://doi.org/10.1038/cddis.2016.32)
• 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 A, Kuhlmann JD, Link T, Wimberger P, Browne AJ, Rauner M, Hofbauer LC, Rachner TD
  (See online at https://doi.org/10.1007/s10549-017-4296-3)
• Concurrent antitumor and bone-protective effects of everolimus in osteotropic breast cancer. Breast Cancer Res. 2017;19:92
  Browne AJ, Kubasch ML, Göbel A, Hadji P, Chen D, Rauner M, Stölzel F, Hofbauer LC, Rachner TD
  (See online at https://doi.org/10.1186/s13058-017-0885-7)