AQP5: A functional gastric cancer stem cell marker in mouse and human tumors
- Hui Yi Grace Lim
- Swathi Yada
- Kazuhiro Murakami
- Bernett Teck Kwong Lee
- Sowmya Sagiraju
- Phyllis Phuah
- Tanysha Chi-Ying Chen
- Fidelia B. Alvina
- Si Hui Tan
- Kaushal Krishna Kaslikar
- Nur Syahirah Binte Ruhazat
- Menaka Priyadharsani Rajapakse
- Katzrin Bte Ahmad Murad
- Snezhina Kancheva
- Liang Thing Tan
- Seri Mustafah
- Jimmy Bok Yan So
- Nick Barker
2025-12-18
Cancer stem cells (CSCs) represent a self-renewing population capable of fueling long-term tumor growth. In gastric cancer, the identity of CSC populations remains unclear. In this study, we established a gastric CSC population marked by the water channel protein aquaporin-5 (AQP5), which resides in human and mouse pyloric tumors. Using multiple organoid and mouse models, we found a requirement for AQP5 + CSCs in both initiating and sustaining cancer progression and demonstrated that AQP5 expression also directly promotes tumor growth and invasion in a WNT, PI3K (phosphatidylinositol 3-kinase), and MAPK (mitogen-activated protein kinase)–dependent manner. Beyond primary cancers, AQP5 further enriches for a functional CSC population in metastatic tumors. Together, our findings support a CSC model in gastric tumors that may have application for therapeutic strategies targeting CSCs.