Wnt Signaling

in Cancer and Stem Cells

Wnt Signaling and Cancer     

Wnt signaling is essential for development, tissue homeostasis, and regeneration. However, hyperactivation of Wnt signaling leads to human disease including cancer. Thus, blockade of Wnt signaling will be the potential therapeutic approaches for cancer treatment. However, due to the crucial roles of Wnt signaling in tissue stem cell maintenance and activation, targeting Wnt signaling is still challenging. To tackle this problem, we are addressing the following questions: How do we manipulate Wnt signaling for disease treatment? How can cancer-specific Wnt signaling regulators be therapeutically targeted?

 

 

Identifying and Targeting Cancer-Specific Wnt Signaling Regulators

Many human cancers harbor genetic or epigenetic deregulation of the key components of Wnt signaling. This setting hyperactivates Wnt/beta-catenin target gene expression (c-Myc, Cyclin D1, etc.), which results in the tumor initiation, proliferation, and metastasis. Intriguingly, despite the homogenous mutations of tumor cells, the activity of Wnt/beta-catenin signaling in tumors is heterogeneous, which is called 'beta-catenin paradox'. Moreover, many recent reports including ours strongly suggest that even Wnt/beta-catenin signaling mutated cells can be negatively controlled by the specific manipulation of Wnt/beta-catenin signaling. Based on the beta-catenin paradox concept, we have sought to identify cancer-specific Wnt signaling regulators. Our comprehensive approaches unveiled the cancer-specific Wnt signaling regulators (Mol Cell 2013, Cell Reports 2013, Nat Comms 2016a, Nat Comms 2016b). Furthermore, we found that genetic ablation (knock-out) of these genes significantly inhibits tumor initiation and proliferation in mouse models. Currently, we are developing the ways to manipulate such Wnt signaling regulators as the new regime of cancer treatment. 


Related publications

Jung et al., Nature Cell Biology 2018a

Jung et al., Nature Cell Biology 2018b

Kim et al., Developmental Cell 2018

Suh et al., Cell Reports 2017

Suh et al., Scientific Reports 2016

Jung et al., Oncotarget 2016

Jun et al., Nature Communications 2016

Wang et al., Nature Communications 2016

Wang et al., Developmental  Cell 2015

Jung et al., Molecular Cell 2013

Jun et al., Cell Reports 2013

Park et al., Nature 2009

Park et a., Developmental Cell 2006

Park et al., Developmental Cell 2005

Kim et al., Nature Cell Biology 2004