Pfister lab - research

Molecular mechanisms of tumor biology

Mechanisms regulating cell growth, proliferation and survival play a crucial role in development and disease. Wnt/b-catenin signaling drives the expression of target genes regulating e.g. proliferation, migration and apoptosis. De-regulation of Wnt signaling has severe consequences leading to tumors, for instance colon cancer and leukaemia. In contrast, increasing evidence suggests that Wnt/b-catenin signaling is down-regulated during aging, e.g. in haematopoietic stem cells.

Our research aims to better understand the cellular and molecular mechanisms underlying tumor growth and survival. Thus, we currently focus on Wnt target genes that give rise to hallmarks of tumor development and aging when being mis-expressed or mutated. We focus on interesting candidates acting as pro-survival factors by use of various molecular biology methods, cell biology, biochemistry and in vitro cell-culture assays on primary, cancer and acute myeloic leukemia (AML) cells. Moreover, we investigate their in vivo function in Xenopus laevis as a potent model organism.

Our research on the Wnt target gene Peter Pan (PPAN).

We previously demonstrated that nucleophosmin (NPM), which is commonly mutated in AML, interacts with Peter Pan (PPAN) (Pfister et al., 2015). Both factors are Wnt target genes and are crucial for cell growth and survival, as they regulate ribosome biogenesis in the nucleolus. In our recent publication we showed that PPAN localizes to mitochondria, PPAN knockdown triggers apoptosis, reduces NPM levels and induces nucleolar stress independently of p53 (Pfister et al., 2015). In contrast, PPAN overexpression made cancer cells more resistant to treatment with chemotherapeutic agents. In our ongoing projects we are elucidating the molecular mechanisms underlying PPAN function in more detail.

Funded by:

Medical Faculity Ulm University, Bausteinprogramm

Deutsche Krebshilfe