When multiple cells are gathered to form tissue, they would communicate with each other to make a decision: what kind of tissue are they going to form? The Notch signaling system allows direct communication between various types of cells in the blood. Recently, scientists from the UCLA Cancer Center revealed for the first time that the mechanical stress generated by the interaction between cells is critical to the programming of the Notch signaling system.
Prior to this study, studies have speculated that cells based on the Notch pathway can pull each other and activate the Notch pathway. Currently, the research findings of scientists was published on the International Famous Magazine Developmental Cell on May 31.
Researcher Weinmaster said their research found the use of an optical tweezers to measure the mechanical stresses of cells jumping to the Notch pathway. Through biochemical and cellular biology analysis, the researchers found that pulling Notch can transport information to construct specific intercellular effects.
Under normal conditions, Notch is folded up and exists in an inactivated form; but once exposed, it activates signal transmission between cells. Ligand cells can pull Notch to initiate interactions between cells. The researchers attempted to obtain evidence that ligand cells can initiate a signal transfer by generating a pull to initiate a reaction between Notch cells. To test this pull, the researchers replaced the Notch cells with beads from Notch, which were captured by laser light and exposed to ligand cells. The researchers said that if the cells can produce mechanical force, they can replace this small beads, and then the mechanical force can be measured.
The study also clearly demonstrated that signaling pathways that activate phagocytosis in cells are unique to Notch. Researcher Meloy-Kapella said that our study provides strong evidence that ligand endocytosis can produce power to pull Notch and recognize a new role in endocytosis in activating cellular signaling pathways. Ligand endocytosis is to generate mechanical stress and ultimately activate the Notch pathway. Future researchers plan to specifically determine the mechanical forces that separate the Notch pathway and visually indicate the mechanical forces that activate the Notch pathway.
Notch signaling pathway and diseases
Notch signaling pathway is found to be linked with many diseases, and the following is just two example.
Notch inhibitors make colon cancer chemotherapy more effective
Recently, the Western Australian Institute of Medical Research (WAIMR) scientists have made exciting discoveries in colon cancer research, which may lead to more effective chemotherapy for colon cancer patients.
The findings have just been published in the new issue of the British Journal of Cancer, which collected 441 tumors from patients with colorectal cancer who underwent surgery and chemotherapy at Sir Charles Gairdner Hospital. The researchers found that when the "Notch signal" gene is turned on in colorectal cancer, the tumor grows rapidly, resulting in a lower survival rate.
WAIMR researcher Dr. Patrick Candy said that the Notch signal that is overexpressed in colon cancer is usually lower in healthy adults. But in studies of colon cancer cell lines, they found that when tumors learned how to turn on Notch signaling, they became more resistant to chemotherapy.
New research suggests that medical professionals can test the levels of these Notch proteins and use it to determine whether a Notch inhibitor drug may help a chemotherapeutic drug work better. Dr. Candy said that although the study has yielded statistically strong results, there is clearly more work to be done to help Notch inhibitor drugs enter clinical practice.
NOTCH gene mutation is associated with lung cancer
Italian researchers have announced that they have discovered a genetic variant associated with lung cancer. Researchers at institutions such as the University of Milan in Italy have found that a genetic variant called NOTCH is associated with lung cancer because the Numb protein responsible for controlling this gene loses control. Studies have shown that the NOTCH gene is mutated in 33% of lung cancer patients. The researchers will continue to conduct clinical trials to study the effects of treatment with the NOTCH gene.
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