Protein “Dilp8/INSL3” and Eating Disorder in Cancer Patients

When you have cancer, it is important to maintain your physical strength to withstand treatment. However, most cancer patients have difficulty maintaining their physical strength due to problems such as nausea and loss of appetite.

Korean researchers have found proteins that cause eating disorders that can significantly improve the effectiveness of chemotherapy in cancer patients.

Dr. Lee Kyu-sun’s research team at the Korea Institute of Biotechnology found a mechanism in which the protein “Dilp8/INSL3” secreted from cancer cells regulates appetite control hormones and identified the cause of eating disorders in cancer patients.

Cancer liquid syndrome, a complication of cancer in cancer patients, is a secondary disease that causes eating disorders and weight loss, resulting in a decrease in muscle and fat tissue and nutritional metabolic imbalance due to increased muscle and fat breakdown. This is known as a representative symptom that adversely affects the survival rate of cancer patients.

“Cancerliquid” is generally known to accompany more than 80% of digestive cancer patients, and eating disorders and weight loss in cancer patients are known to be the direct cause of death in 10-20% of all cancer patients.

The research team confirmed that the expression and secretion of certain proteins “Dilp8” derived from cancer cells is significantly increased through a fruit fly cancer model and RNA transcriptional analysis.

This protein has been shown to alter the expression of appetite-controlled hormones through receptors in brain neurons, leading to eating disorders in the hyperparis cancer model.

In cancer-causing experimental rat models, this “Dilp8” protein and its homologous factor “INSL3” are significantly increased, causing eating disorders, especially when protein “INSL3” secreted by cancer cells is injected directly into the brain of mice.

In addition, Professor Kim Song-cheol’s team at Asan Medical Center in Seoul conducted a clinical association study on pancreatic cancer patients with the highest incidence of bad fluid and found that the concentration of the protein “INSL3” was high in pancreatic cancer patients with eating disorders.

It is expected that the newly identified diagnosis and regulation of proteins will increase the effectiveness of chemotherapy on cancer patients and contribute to the development of metabolic disease treatments.

Source: Yeom, E., Shin, H., Yoo, W. et al. Tumour-derived Dilp8/INSL3 induces cancer anorexia by regulating feeding neuropeptides via Lgr3/8 in the brain. Nat Cell Biol 23, 172–183 (2021).

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