Haematology/Oncology

Department of Internal Medicine I

Group Members

Hendrik Ungefroren (Group leader)
David Witte (MD student)
Julian Hartmann (MD student)
Heike Albrecht (Technician)
Sylvia Grammerstorf-Rosche (Technician)


Research Interests

Project 1: The role of PAR2 and Rac1/Rac1b in TGF-beta-induced tumor progression

The biology of cancer cells is regulated in part by “transforming growth factor (TGF)-beta”. In normal cells and cells of early stages of tumor development this growth factor acts as a tumor suppressor, whereas in later stages it is a potent driver of tumor progression by its ability to enhance neoangiogenesis, desmoplasia and metastasis formation. How this switch is controlled at the molecular level remains speculative. It appears to involve alterations in TGF-beta signaling crosstalk with other pathways’ components, such as the G-protein-coupled receptor PAR2 and the GTPases Rac1 and Rac1b. In this project, we aim to elucidate the molecular basis of the interactions between PAR2/Rac1/Rac1b and TGF-beta signaling.

Project 2: Ionizing radiation and its interaction with the TGF-beta signaling pathway in carcinoma cells

Radiation therapy is a standard treatment form of certain solid tumors. However, it can cause severe collateral damage to adjacent normal tissue eventually resulting in fibrosis and the formation of secondary tumors. Since both processes involve the secretion and activation of TGF-beta, we study the role of TGF-beta and its molecular actions on these radiation-induced side effects.

Project 3: Interaction of clinically used Src-inhibitors with TGF-beta signaling

We demonstrated previously that some clinically used inhibitors of the SRC oncogene turned out to be potent inhibitors of TGF-beta-dependent responses, suggesting that their antitumor effects are based in part on their ability to interfere with TGF-beta signaling. In this project we aim to identify and characterize the molecular targets of this cross-inhibition.  


Collaborations

  • Roland Kaufmann, University Hospital Jens, Germany
  • Susanne Sebens, Institut für Experimentelle Tumorforschung, Kiel, Germany


Latest Publications

  1. Ungefroren H, Groth S, Sebens S, Lehnert H, Gieseler F, Fandrich F: Differential roles of Smad2 and Smad3 in the regulation of TGF-beta1-mediated growth inhibition and cell migration in pancreatic ductal adenocarcinoma cells: control by Rac1. Mol Cancer. 2011;10:67.
  2. Mandel K, Seidl D, Rades D, Lehnert H, Gieseler F, Hass R, Ungefroren H. Characterization of spontaneous and TGFβ-induced cell motility of primary human normal and neoplastic mammary cells in vitro using novel real-time technology. PLoS One. 2013;8:e56591.
  3. Ungefroren H, Sebens S, Giehl K, Helm O, Groth S, Fandrich F, Röcken C, Sipos B, Lehnert H, Gieseler F. Rac1b negatively regulates TGF-beta1-induced cell motility in pancreatic ductal epithelial cells by suppressing Smad signalling. Oncotarget. 2014;5:277-90.
  4. Carl C, Flindt A, Hartmann J, Dahlke M, Rades D, Dunst J, Lehnert H, Gieseler F, Ungefroren H. Ionizing radiation induces a motile phenotype in human carcinoma cells in vitro through hyperactivation of the TGF-beta signaling pathway. Cell Mol Life Sci. 2016;73:427-43,
  5. Bartscht T, Rosien B, Rades D, Kaufmann R, Biersack H, Lehnert H, Gieseler F, Ungefroren H. Dasatinib blocks transcriptional and promigratory responses to transforming growth factor-beta in pancreatic adenocarcinoma cells through inhibition of Smad signalling: implications for in vivo mode of action. Mol Cancer. 2015;14:199.