AG Prof. Dr. von Wichert

Leader

Prof. Dr. Götz von Wichert

Current members:

PhD students
Heidrun Schmid
Denis Krndija

Technicians
Füsun Gökmen
Jasmine Eismann

Medical thesis students
Kerstin Bucher
Teresa Edenfeld

Group (f.l.t.r.): Denis Krndija, Füsun Gökmen, Heidrun Schmid, Jasmine Eismann, Götz von Wichert

 Matrix Forces on the Cytoskeleton Act as Critical Signals

Cell interactions with the extracellular matrix (ECM) and with neighboring cells trigger numerous responses that play essential roles in regulating their behavior and fate. ECM adhesion and assembly affect cells in many ways: Since the ECM provides the physical microenvironment in which cells live, it provides a substrate for cell anchorage, serves as a tissue scaffold and guides cell migration during embryonic development and systemic dissemination of cancer cells. However, beyond these obvious scaffolding functions, the ECM is also responsible for transmitting environmental signals to cells that affect essentially all aspects of a cell's life, including its proliferation, differentiation, and death. Thus, not only is the molecular composition of the ECM important, but also its topography and mechanical properties. Therefore, a cell's life in the ECM appears to involve intense and complex cross-talk with the matrix and it is increasingly accepted that basically all cells actively and continuously sense matrix forces .

Fig.1: Changes in the mechanical surrounding or in the contractility induce cellular responses on a biochemical level
(modified from Geiger et al, 2001).

Fig. 2: Human neuroendocrine tumor cells stained for actin and chromogranin A.

However, the mechanisms that allow the sensing of matrix forces are only poorly characterized. In addition, the role of the biophysical properties of the matrix for tumor-host interaction is largely unknown and the contribution of force sensing to the metastatic process is basically undefined. Our lab currently focuses on 1) the molecular basis force sensing, 2) coordination of motility, 3) the force-dependent signaling mechanisms and 4) the role of force sensing in regulating cancer cell migration and metastasis.

Regulation of growth and secretion in gastrointestinal neuroendocrine tumors

The majority of carcinoid tumors are slow-growing tumors that are classified as neuroendocrine or amine precursor uptake and decarboxylation tumors. Carcinoid tumors may arise from various sites, most commonly the gastrointestinal tract and the lung. Carcinoid tumors, except those originating in the rectum, produce a variety of endocrine substances, the most frequent of which are serotonin and kallikrein. The mechanisms regulating growth and hypersecretion are only poorly characterized in this rare type of tumors.
Our group currently analyzes the signal transduction mechanisms controling 1) secretory vesicle biogenesis and transport of vesicles to the site of release and 2) autocrine stimulated growth.

Selected publications

von Wichert G, Haeussler U, Greten FR, Kliche S, Dralle H, Bohm BO, Adler G, Seufferlein T. Regulation of cyclin D1 expression by autocrine IGF-I in human BON neuroendocrine tumor cells. Oncogene. 2005 Feb 10;24(7):1284-9.

von Wichert G, Haimovich B, Feng GS, Sheetz MP. Force-dependent integrin-cytoskeleton linkage formation requires downregulation of focal complex dynamics by Shp2. EMBO J. 2003 Oct 1;22(19):5023-35.

Beil M, Micoulet A, von Wichert G, Paschke S, Walther P, Omary MB, Van Veldhoven PP, Gern U, Wolff-Hieber E, Eggermann J, Waltenberger J, Adler G, Spatz J, Seufferlein T. Sphingosylphosphorylcholine regulates keratin network architecture and visco-elastic properties of human cancer cells. Nat Cell Biol. 2003 Sep;5(9):803-11.

von Wichert G, Jiang G, Kostic A, De Vos K, Sap J, Sheetz MP. RPTP-alpha acts as a transducer of mechanical force on alphav/beta3-integrin-cytoskeleton linkages. J Cell Biol. 2003 Apr 14;161(1):143-53.

von Wichert G, Jehle PM, Hoeflich A, Koschnick S, Dralle H, Wolf E, Wiedenmann B, Boehm BO, Adler G, Seufferlein T Insulin-like growth factor-I is an autocrine regulator of chromogranin A secretion and growth in human neuroendocrine tumor cells. Cancer Res. 2000 Aug 15;60(16):4573-81.