AQP5: A functional gastric cancer stem cell marker in mouse and human tumors
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.
Authors
- Katzrin Bte Ahmad Murad (ORCID: https://orcid.org/0009-0007-1508-7486)
- Bernett Teck Kwong Lee (ORCID: https://orcid.org/0000-0002-2709-1972)
- Kazuhiro Murakami (ORCID: https://orcid.org/0000-0003-1759-9542)
- Fidelia B. Alvina (ORCID: https://orcid.org/0000-0001-7552-1001)
- Si Hui Tan (ORCID: https://orcid.org/0000-0002-0809-0085)
- Sowmya Sagiraju
- Phyllis Phuah (ORCID: https://orcid.org/0000-0003-2355-0358)
- Nur Syahirah Ruhazat (ORCID: https://orcid.org/0009-0008-7709-0530)
- Liang Thing Tan
- Nick Barker (ORCID: https://orcid.org/0000-0003-3566-4475)
- Hui Yi Grace Lim (ORCID: https://orcid.org/0000-0002-3241-9952)
- Menaka Priyadharsani Rajapakse
- Jimmy Bok Yan So (ORCID: https://orcid.org/0000-0002-9772-7905)
- Swathi Yada (ORCID: https://orcid.org/0000-0001-7118-890X)
- Tanysha Chi-Ying Chen (ORCID: https://orcid.org/0009-0005-5323-9765)
- Seri Mustafah
- Snezhina Kancheva (ORCID: https://orcid.org/0009-0008-0264-5570)
- Kaushal Krishna Kaslikar (ORCID: https://orcid.org/0009-0004-2975-986X)
Institutions
- Kanazawa University (JP)
- Agency for Science, Technology and Research (SG)
- National University of Singapore (SG)
- Nanyang Technological University (SG)
- Singapore Immunology Network (SG)
- Khoo Teck Puat Hospital (SG)
- National University Cancer Institute, Singapore (SG)
- Singapore Centre for Environmental Life Sciences Engineering (SG)
- Institute of Molecular and Cell Biology (SG)
Publication Details
- Journal
- Science
- Published
- 2025-12-18
- DOI
- https://doi.org/10.1126/science.adr2428
- Primary Topic
- Ion Transport and Channel Regulation
- Type
- article
- Field-Weighted Citation Impact
- 0.00