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How childhood liver tumor cells acquire different features

16 June 2026

Karin Söderlund Leifler

Researchers from Linköping University and the Princess Máxima Center in the Netherlands have discovered how the so called Wnt signaling pathway can result in tumor cells with different features within a single tumor. Their findings, published in PNAS, contribute to better classification of these tumors and, in the future, more tailored treatments.

A couple of people sitting at a desk in front of a computer. Photographer: John Karlsson
Researchers from Linköping University and the Princess Máxima Center in the Netherlands have now discovered how the so called Wnt signaling pathway can result in tumor cells with different features within a single tumor.

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 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.

“We 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 ‘molecular partners’ in the pathway that determine how that mutation is interpreted,” says Thomas Kluiver, PhD student research group led by Dr. Weng Chuan Peng at the Princess Máxima Center, in a press release.

He worked closely with Anna Nordin from the laboratory of Professor Claudio Cantù at Linköping University. 

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.

“Because similar regulatory networks operate in many tissues, this mechanism may also help explain how Wnt signaling produces different outcomes in other cancers,”, says Claudio Cantù.

The study was supported by by Cancerfonden, the Swedish Research Council, LiU/RÖ-Cancer, the Knut and Alice Wallenberg Foundation, Oncode Accelerator, Stichting Kinderen Kankervrij and the Princess Máxima Center Foundation, among others.

The article: Differential Wnt/β-catenin signaling via TCF7L2/LEF1 binding specificity shapes cellular and tumor phenotypes, Thomas A. Kluiver, Anna Nordin, Yuyan Lu, Claudio Cantù, Weng Chuan Peng et al., (2026), PNAS, published online June 10 2026. doi: https://doi.org/10.1073/pnas.2528450123

Wnt in hepatoblastoma

  • Hepatoblastoma is the most common form of liver cancer in children. In Sweden, fewer than ten children are diagnosed with the disease each year, while around 4,000 new cases are diagnosed globally.
  • Nearly all hepatoblastomas have a change in the CTNNB1 gene, which activates the Wnt signalling pathway. Despite having the same genetic change, the tumours may contain different cell types.
  • The study shows how Wnt signalling can contribute to different features in tumour cells within the same tumour. This knowledge may help improve tumour classification and, in the longer term, lead to more tailored treatment.

Contact

Photo of Claudio Cantù

Claudio Cantù

Professor
Photo of Anna Nordin

Anna Nordin

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