AQP5: A functional gastric cancer stem cell marker in mouse and human tumors.

Lim, Hui Yi Grace; Yada, Swathi; Murakami, Kazuhiro; Lee, Bernett Teck Kwong; Sagiraju, Sowmya; Phuah, Phyllis; Chen, Tanysha Chi-Ying; Alvina, Fidelia B et al. · Science · 2025

basic_science · Level V

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Abstract

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<sup>+</sup> 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.

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