How cells communicate and develop is controlled by communication pathways. The Wnt signaling pathway plays a central role in almost all childhood liver tumors.
The most common form of liver cancer in children聽is hepatoblastoma. In Sweden, less than ten children are diagnosed with the disease each year. Globally, around 4,000 new cases are diagnosed yearly. Being a rare disease, hepatoblastoma is seldom the focus of research.
Nearly all hepatoblastomas carry a change in the same gene, CTNNB1. This is the key activator of the Wnt signaling pathway.
Yet despite sharing common genetic driver CTNNB1, these tumors often contain two main cell types: the fetal type, that is more differentiated, and the less differentiated embryonal type. Researchers expect that the way the tumor is composed of these two cell types influences the effectiveness of chemotherapy treatment. Classification based on tumor composition could thus play an important role to provide children with liver cancer with more tailored treatments.
Better understanding of tumor diversity
Using lab grown patient-derived mini liver tumors and advanced genomic technologies, the researchers uncovered how activation of the Wnt pathway causes these two distinct tumor features.
鈥淲e found that the same change in DNA can lead to different cell types, depending on which biological programs are active in a cell. It is not just the mutation itself, but also the 鈥榤olecular partners鈥� in the pathway that determine how that mutation is interpreted,鈥� says Thomas Kluiver, PhD student research group led by Dr. Weng Chuan Peng at the Princess M谩xima Center, in a press release.
He worked closely with Anna Nordin from the laboratory of Professor Claudio Cant霉 at Link枚ping University.聽
Because Wnt signaling plays an important role in many types of cancer in both children and adults, these findings may also be relevant for other researchers.
鈥淏ecause similar regulatory networks operate in many tissues, this mechanism may also help explain how Wnt signaling produces different outcomes in other cancers,鈥�, says Claudio Cant霉.
The study was supported by by Cancerfonden, the Swedish Research Council, LiU/R脰-Cancer, the Knut and Alice Wallenberg Foundation, Oncode Accelerator, Stichting Kinderen Kankervrij and the Princess M谩xima Center Foundation, among others.
The article: , Thomas A. Kluiver, Anna Nordin, Yuyan Lu, Claudio Cant霉, Weng Chuan Peng et al., (2026), PNAS, published online June 10 2026. doi: https://doi.org/10.1073/pnas.2528450123
