Department of Internal Medicine I

Group Members

Hendrik Ungefroren (Group leader)
Heike Albrecht (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.  


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

Latest Publications

  1. Negative Control of Cell Migration by Rac1b in Highly Metastatic Pancreatic Cancer Cells Is Mediated by Sequential Induction of Nonactivated Smad3 and Biglycan.

    Otterbein H, Lehnert H, Ungefroren H.

    Cancers (Basel). 2019 Dec 6;11(12). pii: E1959.

  2. RAC1B: A Guardian of the Epithelial Phenotype and Protector Against Epithelial-Mesenchymal Transition.

    Zinn R, Otterbein H, Lehnert H, Ungefroren H.

    Cells. 2019 Dec 4;8(12). pii: E1569.

  3. Different signaling and functionality of Rac1 and Rac1b in the progression of lung adenocarcinoma.

    Seiz JR, Klinke J, Scharlibbe L, Lohfink D, Heipel M, Ungefroren H, Giehl K, Menke A.

    Biol Chem. 2019 Dec 27. pii: /j/bchm.ahead-of-print/hsz-2019-0329/hsz-2019-0329.xml.

  4. Potential Role of MSC/Cancer Cell Fusion and EMT for Breast Cancer Stem Cell Formation.

    Hass R, von der Ohe J, Ungefroren H.

    Cancers (Basel). 2019 Sep 25;11(10). pii: E1432.

  5. RAC1B Suppresses TGF-β-Dependent Chemokinesis and Growth Inhibition through an Autoregulatory Feed-Forward Loop Involving PAR2 and ALK5.

    Otterbein H, Mihara K, Hollenberg MD, Lehnert H, Witte D, Ungefroren H.

    Cancers (Basel). 2019 Aug 20;11(8). pii: E1211.