growth protein called Notch1-a protein that acts like a cellular communicator, helping cells decide what to do, such as grow, divide, or take on specific roles. It is part of the Notch signalling pathway, which is crucial during early development and in maintaining healthy tissues. Notch1 becomes active when it interacts with specific proteins on neighbouring cells. This triggers a series of “cuts” in the protein, releasing the Notch1 intracellular domain (NICD).
NICD travels to the nucleus, where it switches on genes that drive cell growth, division, and survival. When Notch1 is overactive or stabilised, it can cause uncontrolled cell growth and contribute to cancer. In CRC, high levels of active Notch1 are linked to a poorer prognosis because it drives tumor growth and helps cancer cells survive longer. To keep Notch1 activity in check, it must be phosphorylated (marked for destruction) and broken down by the cell’s “recycling system.” If this balance is disrupted, Notch1 can remain active for too long and promote cancer growth.
The research was led by Associate Professor Zhang Yongliang, from the Department of Microbiology & Immunology, and Immunology Translational Research Programme (TRP), NUS Medicine. A/Prof Zhang said, “In CRC, higher levels of DUSP6 have been found in tumors, where it helps cancer cells grow faster, spread more easily, and leads to poorer outcomes for patients. This unexpected role highlights why DUSP6 is now seen as a possible target for new treatments. Our research not only explains why some colon cancers are so aggressive, but also gives us a clear target to develop new treatments.”
The study found that DUSP6 protects cancer cells by inhibiting a process that normally destroys a key growth protein called Notch1-a protein that acts like a cellular communicator, helping cells decide what to do, such as grow, divide, or take on specific roles. It is part of the Notch signalling pathway, which is crucial during early development and in maintaining healthy tissues. Notch1 becomes active when it interacts with specific proteins on neighbouring cells. This triggers a series of “cuts” in the protein, releasing the Notch1 intracellular domain (NICD).
NICD travels to the nucleus, where it switches on genes that drive cell growth, division, and survival. When Notch1 is overactive or stabilised, it can cause uncontrolled cell growth and contribute to cancer. In CRC, high levels of active Notch1 are linked to a poorer prognosis because it drives tumor growth and helps cancer cells survive longer. To keep Notch1 activity in check, it must be phosphorylated (marked for destruction) and broken down by the cell’s “recycling system.” If this balance is disrupted, Notch1 can remain active for too long and promote cancer growth.
The potential for a novel therapy for colorectal cancer (CRC) may be realized through the inhibition of DUSP6. In experimental models, scientists demonstrated a significant reduction in tumor growth by obstructing this protein. Elevated levels of DUSP6 are associated with poorer survival rates, suggesting its utility in predicting the aggressiveness of a patient’s cancer. Although the primary focus of the study was CRC, the implications of these findings may extend to other malignancies where DUSP6 is implicated.
The research team intends to investigate further into the pathogenesis of CRC and to develop targeted therapies aimed at DUSP6, with the goal of enhancing health outcomes for patients.
