Researchers in Korea have found that diabetes is remembered by a specific tumor promoter (Nrg1) in cancer cells and is involved in cancer resistance and recurrence.
UNIST (President Lee Yong-Hoon Lee) Department of Life Sciences Professor Ji-Young Park’s research team presented the results of a study on the mechanism of the Nrg1 (Neuregulin 1) regulatory pathway, which plays an important role in the process of malignant tumor development. breast cancer caused by diabetes.
Nrg1 is a glycoprotein belonging to the epidermal growth factor, and is known to act as a growth factor that helps cancer growth. According to previous studies, the activity of the Nrg1 enhancer increases in breast cancer cells with hyperglycemia, and by this, the expression of Nrg1 increases. However, the mechanism for increased Nrg1 expression due to hyperglycemic stimulation has not been clearly elucidated.
Through proteomic analysis of breast cancer cells, the research team found that the RBPJ protein binds to the Nrg1 enhancer region of breast cancer cells exposed to high glycemic stimuli. We also verified that it is regulated by the activation of the Notch signaling pathway.
First, through Notch activation, histone proteins and proteins that regulate biochemical degradation bind to the Nrg1 enhancer region. As a result, changes occur in the chromatin structure of the Nrg1 enhancer, leading to increased Nrg1 gene expression.
In addition, it was confirmed that when the Notch signaling system was inhibited by hyperglycemic stimulation, the expression of Nrg1 was reduced and the growth rate of cancer was reduced accordingly. In addition, it was confirmed that the anticancer effect of the targeted anticancer drug Lapatinib could be enhanced by administering a Notch inhibitor in a hyperglycemic breast cancer mouse model.
Professor Park Ji-young said, “Although the number of diabetic patients is increasing rapidly worldwide and diabetes significantly reduces the survival rate of cancer patients, it is difficult to provide differentiated treatment to cancer patients with diabetic complications due to lack of mechanistic studies. to explain this phenomenon. “The results of this study reveal that the phenomenon of diabetes is remembered by a specific tumor promoting factor (Nrg1) in cancer cells and that it is involved in anti-cancer resistance and the recurrence of cancer cells, thereby opening the possibility of developing targeted therapies according to the metabolic state of cancer patients,” he said.
The results of this study were published on January 27, 2023 in the world-renowned academic journal Nature Communications.
