- Asymmetric Wnt signals of Daam proteins regulate the differentiation of adult intestinal stem cells, affecting the likelihood of tumors

- The result of an international collaborative study between the Catholic University of Korea, the Institute of Molecular Biotechnology (IMBA) in Austria, and the Institute for Basic Science(IBS)

- Study results were published in the internationally renowned journal, “Science Advances, IF 13.6”

* Figure Description: In an organoid test to investigate the role of Daam proteins, Paneth cells increased in the absence of Rnf43, whereas Paneth cells decreased in the absence of Daam (Daam1, Daam2) proteins.

A research team led by Professor Ji-hoon Kim of the Department of Biomedical Sciences of the Catholic University of Korea(President Fr. Luke Won Jong-chul) found the mechanism to regulate Wnt signals, which are closely related to the development of tumors.  They discovered that the cell differentiation of adult intestinal stem cells relies on the asymmetric regulation of Wnt signaling by Daam (Daam1, Daam2) proteins.

Excess cell differentiation of adult stem cells that regenerate the body can lead to the occurrence of tumors, and the intensity of the Wnt signaling system determines the degree of the differentiation of adult stem cells. Professor Ji-hoon Kim’s research team identified the roles of two proteins, △Rnf43 △Daam, that affect the Wnt signaling pathway through the CRISPR tool, also known as genetic scissors.

The research team applied various state-of-the-art experimental techniques such as Mouse Genetics, organoids, and single-cell sequencing to determine the role of Daam proteins. As a result, they confirmed that Rnf43 and Daam proteins control the Wnt signal by removing the Wnt protein receptor on the cell surface. On the other hand, in the absence of Rnf43 and Daam proteins, Wnt signals are over-activated, resulting in excessive proliferation and differentiation of adult stem cells and an increased likelihood of tumor development.

In addition, the research team found that Daam proteins have an asymmetric role in activating the non-canonical pathway of Wnt signaling and deactivating the canonical pathway. In the presence of only Daam proteins, without Rnf43, the non-canonical pathway of Wnt signaling was activated and resulted in excessive Paneth cells. The research team considered it essential to suppress the activation of the non-canonical Wnt signaling pathway by Daam proteins, as the possibility of tumor cell differentiation increases when the non-canonical pathway of Wnt signaling is activated.

 The results of the international collaborative study conducted by a research team led by Professor Ji-hoon Kim of the Department of Biomedical Sciences of the Catholic University of Korea, the Institute of Molecular Biotechnology (IBMA) in Austria, and the Institute of Basic Science (IBS), were published in the internationally renowned journal, “Science Advances, IF 13.6.”

Professor Ji-hoon Kim of the Department of Biomedical Sciences of the Catholic University of Korea said, "Existing anti-carcinogenic drugs related to Wnt signaling have been studied and developed focusing on the canonical pathway of the Wnt signaling." He added, "As the study revealed that the asymmetry of Daam proteins has a direct impact on the regulation of Wnt signaling involved in the development of tumors, it is expected that more profound research on the non-canonical pathway of the Wnt signaling and the development of relevant anti-carcinogenic drugs will be actively carried out in the future." (End of Document)