Hui Yi Grace Lim, Swathi Yada, Kazuhiro Murakami, Bernett Lee, Sowmya Sagiraju, Phyllis Phuah, Tanysha Chi-Ying Chen, Fidelia B. Alvina, Si Hui Tan, Kaushal Krishna Kaslikar, Nur Syahirah Ruhazat, Menaka Priyadharsani Rajapakse, Katzrin Bte Ahmad Murad, Snezhina Kancheva, Liang Thing Tan, Seri Mustafah, Jimmy Bok Yan So, Nick Barker
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.