An integral aspect of our work is to better understand how aberrant cell-cell communication leads to disease. Cancer is the scourge of modern society and our lab is involved various translational research efforts that are tackling this challenge. For example, dysregulated Wnt signaling is implicated in the etiology of many cancer types. A prominent case is colorectal cancer in which mutations that activate Wnt signaling are archetypal gatekeeper mutations; however the role of Wnt signaling in later stages of tumor progression is poorly understood. One focus we have is to close this gap.
Another initiative is the URPP Translational Cancer Research.
URPP Translational Cancer Research
We are involved in the University of Zürich research priority program (URPP) “Translational Cancer Research”. This initiative builds a bridge between fundamental and clinical research and fosters the communication and collaboration between research groups investigating different aspects of cancer. Within this program we currently have a project looking at the roles of β-catenin in squamous cell carcinoma. Squamous cell carcinoma (SCC) is one of the most frequent non-melanoma skin cancers and often occurs in sun-exposed regions of the skin. SCC is often cured surgically, but it relapses in 8% of patients and ca. 5% of patients develop metastasis with poor prognosis. Recently, canonical Wnt signaling was shown to be important for the initiation and development of SCC. Within the proposed project we are specifically addressing the role of the b-catenin transcriptional output for the development of SCC. Our results will help to establish better and efficient therapeutic approaches for SCC treatment combining both immunomodulation and altering Wnt//b-catenin signalling.
A Drosophila tumor model
While our work on tumorigenesis has focused on using genetically engineered mouse models we are also applying the power of Drosophila genetics. We have used a neoplasia model in the fruit fly to identify genes required for tumor growth in vivo. A Drosophila tumor model allows us to rapidly explore the interactions among cancer mutations, and between cell populations that mimic the tumor microenvironment. We have found that tumor cells become dependent on PI3K function and that reduction of PI3K activity synthetically interferes with tumor growth. We have also unearthed the transcription factor Ets21C as a pivotal regulator of tumor growth – it acts as a novel player in transcriptional program controlled by the JNK pathway. Ongoing work is revealing further exciting insights.
Willecke, M., Toggweiler, J., and Basler, K. (2011). Loss of PI3K blocks cell-cycle progression in a Drosophila tumor model. Oncogene 30, 4067-4074.