Li lab

Stem Cell and Cancer Biology Laboratory

 Wnt activating mechanism in colorectal cancers

Intestinal stem cell culture

Colorectal cancer (CRC) is one of the leading causes of cancer death in the world. Aberrant Wnt signal activation is the hallmark of CRC, and is therefore an attractive target for therapeutic intervention. We investigate the Wnt regulatory mechanism in different CRC subtypes with the emphasis on identifying novel tumour-specific targets to improve cancer treatment.

Despite the substantial effort put on therapeutic development of Wnt inhibitors in the past two decades, there is still no approved drug available in the clinic to target Wnt signalling. One major challenge of drugging the Wnt pathway is the toxicity due to its crucial role in normal development and adult tissue homeostasis.

Loss of the negative Wnt pathway regulator APC occurs in the majority of CRC. We have recently identified USP7 as a novel tumour-specific target for APC-mutated CRCs. We showed that a deubiquitinating enzyme USP7 is responsible for β-catenin deubiquitination and stabilisation exclusively in APC-mutated colon cancer cells, which can be used as tumour-specific drug target.

Schematic diagrams showing Wnt activating mechanisms under normal and cancer conditions.
Schematic diagrams showing Wnt activating mechanisms under normal (left, middle) and cancer (right) conditions.

We are currently investigating alternative Wnt activating mechanisms in other non-APC mutated CRC subtypes. We aim to identify tumour-specific drug targets for individual CRC subtypes, which will aid the development of targeted therapy in the clinic.