Singapore scientists identify markers of key stem cell populations driving colorectal cancer formation

SINGAPORE — Researchers from A*STAR Institute of Molecular and Cell Biology (A*STAR IMCB), led by an internationally recognised stem cell expert, have identified markers of two critical stem cell populations that drive colorectal cancer formation. The breakthrough study, published in Nature Cell Biology, reveals how NOX1 and NPY1R proteins mark distinct stem cell populations in different colon regions that serve as the origins of colorectal cancer, providing new targets and models for developing region-specific cancer treatments.

Colorectal cancer is currently the third most diagnosed cancer and second most lethal cancer worldwide, with Singapore recording amongst the highest rates globally. The disease presents significant challenges because cancers arising in different parts of the colorectum — from the caecum to the rectum — show distinct characteristics, treatment responses, and patient outcomes.

Breakthrough Reveals Regional Cancer Origins

Using advanced research techniques and single-cell analysis, the A*STAR IMCB team discovered that NOX1 marks stem cells predominantly in the caecum (the first part of the large intestine), while NPY1R identifies stem cell populations specifically in the lower colon regions. When these stem cells undergo genetic changes, they become the starting points for colorectal cancer development.

The researchers developed new laboratory models that can selectively trigger colorectal cancer formation in specific colon regions by targeting these stem cell populations, providing a more relevant model of human cancer development. This breakthrough addresses a major limitation in current colorectal cancer research, where existing animal models with limited regional specificity tend to generate widespread disease, preventing the study of these colorectal cancers at advanced disease stages within its specific local context.

The discovery has important implications for understanding why colorectal cancers behave differently based on their location. Caecum tumours are typically detected at advanced stages and have high rates of lymph node spread, whilst rectal cancers, accounting for 40% of all colorectal cancer cases, can be detected earlier but remain challenging to treat.

"These findings provide crucial insights into the regional differences we see in colorectal cancer," said Prof Nick Barker, Senior Principal Scientist from A*STAR IMCB. "By identifying new stem cell sources of cancer in different colon regions, we can now develop more accurate cancer models for use in identifying new therapeutic targets, diagnostic markers and evaluating new treatments."

Leading Expert Drives Cancer Research Forward

Prof Barker is a leading authority in gastrointestinal stem cell biology whose work has reshaped how scientists model and target cancers of the digestive tract. In 2007, he led seminal studies published in Nature that identified LGR5 as a definitive marker of adult intestinal stem cells, work that unlocked advanced laboratory technologies now standard in cancer research worldwide. His contributions have been recognised internationally, including the 2022 Japanese Cancer Association International Award for his impact on stem-cell research and cancer biology.

Building on that foundation, Prof Barker's team in 2020 identified Aquaporin-5 (AQP5) as a gastric stem cell marker, enabling the isolation of human gastric stem cells and advancing understanding of gastric cancer origins. Prof Barker's work has been referenced tens of thousands of times by scientists globally, and he has been recognised among the world's top 2% most-cited scientists for six consecutive years (2020–2025) in the Stanford University–Elsevier global ranking.

The new Nature Cell Biology study extends this trajectory by creating the field's first region-specific, stem-cell-initiated colon cancer models, a powerful platform for discovering new treatments and evaluating targeted therapies against different types of colorectal cancers.

Path to Precision Medicine

The research team is now working to validate findings in human colorectal cancer patients and develop new screening approaches using the identified stem cell markers. The breakthrough could lead to personalized prevention and treatment plans based on the region of the colon at risk. For example, doctors could eventually monitor patients with pre-cancerous lesions in different colon regions more precisely, or develop region-specific therapies that target the particular cancer-initiating stem cell populations driving tumor growth in each location of the colon.

This approach represents a shift toward precision oncology for colorectal cancer, where treatments could be tailored to a tumor's cellular origin or unique region-specific cancer markers rather than using one-size-fits-all approaches. Such advances hold promise for reducing the burden of colorectal cancer in Singapore and around the world, potentially saving lives through earlier detection and more effective, targeted treatment options.

Study Citation: Gasnier, M., Chen, T.C.-Y., Yada, S. et al. NOX1 and NPY1R mark regional colon stem cell populations that serve as cancer origins in vivo. Nature Cell Biology (2025). https://doi.org/10.1038/s41556-025-01763-1

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Owen Sia
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Email: owen_sia@a-star.edu.sg

About A*STAR Institute of Molecular and Cell Biology (A*STAR IMCB)

The A*STAR Institute of Molecular and Cell Biology is a premier research institute whose mission is to harness biology for transformational bio-therapeutics and diagnostics. With a strong emphasis on collaboration with stakeholders across the ecosystem in Singapore, A*STAR IMCB aims to achieve scientific excellence and continues to nurture the next generation of scientists in order to create growth and enhance lives. For more information about IMCB, please visit www.a-star.edu.sg/imcb.

About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector R&D agency. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit the economy and society. As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by improving societal outcomes in healthcare, urban living, and sustainability. A*STAR plays a key role in nurturing scientific talent and leaders for the wider research community and industry. A*STAR’s R&D activities span biomedical sciences to physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis. For ongoing news, visit www.a-star.edu.sg.

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