Ligand-dependent Wnt signaling promotes gastric cancer metastasis through hyaluronan expression in microenvironment - PubMed
7 days ago
- #hyaluronan
- #Wnt signaling
- #gastric cancer
- Ligand-dependent Wnt signaling promotes gastric cancer metastasis through hyaluronan expression in the microenvironment.
- Mice with Kras, Tgfbr2, and Trp53 mutations (KTP) develop gastric metaplasia, while those with additional Wnt1 expression (WKTP) develop dysplastic tumors.
- WKTP-derived organoids form liver metastases after splenic transplantation, unlike KTP organoids.
- Apc disruption does not induce metastasis in KTP cells, indicating stromal Wnt signaling's role in metastasis.
- Tumor-derived Wnt ligands cooperate with TGFβ signaling to induce Has2 expression in cancer-associated fibroblasts (CAFs), leading to hyaluronan accumulation.
- Hyaluronidase expression in WKTP cells significantly suppresses liver metastasis.
- The study highlights the potential therapeutic strategy targeting ligand-dependent Wnt signaling and hyaluronan deposition in gastric cancer metastasis.