#Japan #gastric cancer #Kanazawa University #Kanazawa #Wnt signaling

Understanding the Role of Wnt Signaling in Gastric Cancer Spread

Researchers from Kanazawa University's Cancer Research Institute and the Nano Life Science Institute (WPI-NanoLSI) have made significant strides in understanding the mechanisms behind gastric cancer metastasis. The team, led by Masanobu Oshima, unveiled how cancer cells exploit Wnt signaling to reshape surrounding tissues, facilitating the spread of cancer to distant organs such as the liver.

Key Findings

Gastric cancer is notoriously difficult to treat, primarily due to its propensity to metastasize. While genetic mutations underlying gastric tumors have been well-documented, the precise biological processes enabling these tumors to colonize new sites remained elusive. The research highlights that Wnt signaling, a crucial pathway for stem cell maintenance and tissue regeneration, is activated in gastric cancer not through mutations but through external stimulation. This study emphasizes the importance of Wnt signaling within the tumor microenvironment, showcasing its pivotal role in disease progression.

Mechanism of Metastasis

Through advanced mouse and organoid models, the team explored how gastric cancer cells interact with the liver environment. Their research unveiled a series of processes detailing how cancer cells secrete Wnt ligands that stimulate surrounding stromal fibroblasts. This signaling activates the fibroblasts and works in concert with TGF-β signaling pathways, leading to the production of hyaluronan. The accumulation of hyaluronan in metastatic sites creates a supportive microenvironment that not only allows cancer cells to survive but also promotes their growth.

Moreover, the researchers found that simply activating Wnt signaling in cancer cells was not enough to drive metastasis. Instead, it became clear that the activation of Wnt signaling in surrounding stromal cells was crucial for the establishment and survival of metastatic tumors.

Implications for Future Therapies

The discoveries made in this study present potential therapeutic targets aimed at inhibiting gastric cancer progression. The researchers suggest strategies such as:

• - Targeting ligand-dependent Wnt signaling pathways
• - Inhibiting hyaluronan production
• - Disrupting the formation of supportive metastatic niches

By focusing on these mechanisms, medical professionals may develop innovative strategies to prevent metastasis or at least limit its progression.

Contributing to Cancer Research

This groundbreaking research underscores the necessity of understanding the interactions between cancer cells and their microenvironment. By shedding light on how tumor cells manipulate surrounding tissues to enhance their invasive capabilities, scientists can better strategize against gastric cancer metastasis. Future investigations will aim to validate these mechanisms within human tumors and seek effective treatments that can target the tumor microenvironment directly.

As Oshima poignantly states, "Our study shows that metastasis is driven not only by cancer cells themselves, but by how they reshape the surrounding tissue." This insight could pave the way for novel therapeutic approaches that disrupt these supportive environments rather than solely targeting cancer cells.

Conclusion

The findings from Kanazawa University provide a new perspective on the complex dynamics of cancer metastasis, illustrating the interplay between tumor cells and their microenvironment. As we advance our understanding of gastric cancer, the hope remains that targeted therapies can be developed to improve patient outcomes and combat this formidable disease.

For further details, refer to the full study published in Nature Communications on February 14, 2026.