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

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

Science

10.1126/science.adr2428

https://doi.org/10.1126/science.adr2428

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

Cancer stem cells, Gastric cancer

18 December 2025

Lim, H. Y. G., Yada, S., Murakami, K., Lee, B. T. K., Sagiraju, S., Phuah, P., Chen, T. C.-Y., Alvina, F. B., Tan, S. H., Kaslikar, K. K., Ruhazat, N. S. B., Rajapakse, M. P., Murad, K. B. A., Kancheva, S., Tan, L. T., Mustafah, S., So, J. B. Y., & Barker, N. (2025). AQP5: A functional gastric cancer stem cell marker in mouse and human tumors. Science, 390(6779). https://doi.org/10.1126/science.adr2428

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.

Publisher Copyright

This research / project is supported by the Ministry of Health National Medical Research Council - Open Fund - Individual Research Grant
Grant Reference no. : OFIRGmay-0069

This research / project is supported by the Ministry of Health National Medical Research Council - Open Fund - Individual Research Grant
Grant Reference no. : OFYIRG22jul-0006

This research / project is supported by the A*STAR - Target Translation Consortium Grant
Grant Reference no. : TTC2019_002

This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on Volume 390, 18 Dec 2025, DOI: 10.1126/science.adr2428

https://oar.a-star.edu.sg/communities-collections/articles/22662

0036-8075
1095-9203

Institute of Molecular and Cell Biology