Colon Cancer Cells Can Change Identity To Spread Faster: Study

Scientists have identified a molecular switch that may explain how colorectal cancer becomes more aggressive. The discovery could help track tumour spread and improve future treatment strategies.

Scientists uncover colon cancer switch.

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• GATA6 levels could predict metastasis risk, guiding treatments.

Scientists have uncovered a molecular switch that could explain why colorectal cancer becomes far more dangerous once it spreads beyond the intestine. The study found that when levels of a gene-regulating protein called GATA6 fall, colon cancer cells lose their normal identity and transform into highly adaptable, fetal-like cells capable of travelling through the bloodstream and forming new tumours in the liver. The research, led by scientists at Weill Cornell Medicine and the Massachusetts Institute of Technology (MIT), suggests that this transformation is driven largely by epigenetic changes changes in how genes are switched on and off rather than new DNA mutations. The findings, published in Cell Stem Cell, could open new avenues for identifying patients at higher risk of metastasis and developing treatments that stop cancer from spreading.

GATA6 Acts As The Cell's Identity Keeper

GATA6 is a transcription factor that helps intestinal cells maintain their specialised identity by regulating which genes remain active. According to the researchers, healthy levels of GATA6 keep colon cells functioning normally. However, the study found that GATA6 levels were significantly lower in liver metastases from both mice and people with colorectal cancer. Patients with reduced GATA6 expression were also found to have poorer clinical outcomes. Once colorectal cancer spreads to distant organs such as the liver, treatment becomes considerably more difficult. Metastasis remains the leading cause of death among people diagnosed with colorectal cancer. For years, scientists searched for specific genetic mutations responsible for liver metastasis, but no single mutation consistently explained the process. Instead, the new findings suggest that changes in gene activity may play a much larger role. Dr. Norihiro Goto, Assistant Professor of Medicine in the Division of Gastroenterology and Hepatology at Weill Cornell Medicine, said the loss of GATA6 acts as a critical switch that converts non-metastatic cancer cells into cells capable of spreading throughout the body.

How Cancer Cells Become More Aggressive

Unlike genetic mutations, epigenetic changes do not alter the DNA sequence itself. Instead, they determine which genes are turned on or off, influencing how cells behave. To understand the earliest stages of metastasis, researchers developed three-dimensional organoids miniature laboratory-grown versions of tumours from liver metastases. These organoids were implanted into mice, allowing scientists to observe how cancer cells gradually evolved into highly aggressive forms capable of spreading. The experiments showed that when GATA6 disappeared, cancer cells became remarkably flexible. Instead of behaving like mature intestinal cells, they reverted to a primitive, fetal-like state that enabled them to survive stressful conditions, travel through the bloodstream, and establish tumours in distant organs. Researchers describe this process as lineage plasticity, a phenomenon in which cells change their identity and function. While this ability normally helps the body repair damaged tissues, cancer cells appear to exploit the same mechanism to spread more efficiently.

Why The Discovery Could Change Future Cancer Care

The researchers also observed that the loss of GATA6 caused tumour cells to lose LGR5, a marker commonly associated with intestinal stem cells. Earlier studies have linked LGR5-negative cells with an increased ability to initiate liver metastases. In contrast, restoring GATA6 activity or activating related biological pathways reduced the ability of colorectal cancer cells to spread in laboratory models.Interestingly, deleting GATA6 had little effect on the size or growth of the original tumour. Instead, it dramatically increased both the number and severity of liver metastases. This suggests that a tumour's ability to spread depends more on changes in cellular identity than on how quickly the primary tumour grows.

What This Means For Future Treatments

The findings suggest that GATA6 could eventually serve as a biomarker to identify patients whose tumours carry a higher risk of metastasis. Measuring GATA6 levels may help doctors decide which patients require closer monitoring or more aggressive treatment before the disease spreads. The research also highlights a promising therapeutic strategy preventing cancer cells from switching into highly adaptable, metastatic states. Scientists caution, however, that this approach will require careful development because similar biological pathways are also essential for normal tissue repair and healing. The research team now plans to identify weaknesses unique to GATA6-deficient cancer cells that could be targeted with future therapies. They also aim to investigate how immune cells and the liver's surrounding environment influence this transformation, with the hope of developing treatments that can stop colorectal cancer before it spreads.

Disclaimer: The information provided in the article is intended for general informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare provider with any questions you may have regarding a medical condition