EMBO Mol Med: Zengmu St. team reveals the molecular mechanism and function of INSL5 regulating tumor sugar metabolism.

!---- different from the energy metabolism of normal cells, tumor cell energy metabolism not only provides energy for tumor cells, but also provides them with biosynthesis raw materials to maintain their rapid proliferation, the tumor's energy metabolism directly determines the fate of tumor cells.cells' energy comes mainly from sugar metabolism, and the ways in which glucose is metabolized in organisms include glycosases and oxidation phosphorylation.cell activity is closely related to its energy state, malignant tumors grow rapidly, often have increased glucose intake, increased activity of glycoenzyme and lactic acid accumulation.the oxygen cells of the tumor, glucose still converts to lactic acid, a metabolize called aerobic glycolysis or the Warburg effect.with the further research, it is found that tumor cells can not only develop aerobic sugar enzyme, but also oxidizing phosphorylation, the two coordinated to produce metabolic symbiosis.tumor-causing DNA virus is the main cause of many malignant tumors, EB virus (Epstein-Barr virus, EBV) as the first identified human tumor-causing virus, including nasopharyngeal cancer in the development of a variety of tumors play an important role.identifying metabolic bridges between tumor-causing virus infection sviral infections and tumor cells can provide new therapeutic targets for tumors associated with tumor-causing viruses.insulin-like peptide 5 (Insulin like 5, INSL5) is an insulin super family member with a classical structure of an insulin family member and its sole receptor has been identified as RXFP4/GPCR142.previousreports have shown that INSL5 is associated with fertility and appetite in mice, and its expression is regulated by energy supply and gut flora.however, its role and function in nasopharyngeal cancer are not yet known.recently, Zeng Musheng/Yu Jianhua/Ling Zhiqiang/Professor Zheng Yuming's team published a research paper on Autocrine INSL5 promotes stumor progression and glycolysis via activation of STAT5 signaling at EMBO Molecular Medicine.the study first reported that EBV infection of the diseased nasopharyngeal epithelial cells led to an increase in insl5 (Insulin-like peptide 5), in which INSL5 and its receptor GPCR142 axis promote the expression of glycoenzyme-related genes by activating the STAT5 signaling pathway in the cell, which in turn affects the reprogramming of glycometabolisaandic metabolism and ultimately promotes the progression of nasopharyngeal cancer.China is the world's high estual cancer area, each year new cases accounted for more than 47% of the world, involving more than 400 million people, including South China and Hong Kong and Macao region the highest incidence (20/100,000 or more), so nasopharyngeal cancer is also known as "Guangdong tumor."EB virus infection is the most important biocarcinogenic factor of nasopharyngeal cancer, Professor Zengmu has been working for many years on the receptor and tumor-causing mechanisms of EB virus infection of epithelial cells.in early studies, the team successfully constructed a model of high-efficiency infection of nasopharyngeal epithelial cells and identified several key host proteins for EBV-infected epithelial cells, including EPHA2, NRP1, and NMHC-IIA, laying an important foundation for fully revealing the mechanisms of EBV infection of epithelial cells and the development of subsequent blocking vaccines.the study found that EBV infection led to an increase in INSL5 expression through an expression spectrum analysis of the model of eBV effective infection of the nasopharyngeal epithelial cells.functional studies have found that INSL5 promotes cell value-added and invasive metastasis, knocking down or using antibodies and its receptor GPCR142 can reverse this phenomenon, showing that INSL5 acts as a pro-tumor function through self-secretion pathways to act on self-receptors. mechanism, INSL5 promotes the expression of glycoenzyme-related genes by activating the STAT5 pathway, which in turn affects the reprogramming of cell sugar metabolism. researchers blocked the binding between INSL5 and receptor GPCR142 by neutralizing antibodies and found that the INSL5-GPCR142 axis could serve as a target for individualized treatment of nasopharyngeal cancer. further use the team's self-research kit to analyze the expression of INSL5 in patients with multicenter large samples of nasopharyngeal cancer and normal human serum, and found that INSL5 is highly expressed in the serum of nasopharyngeal cancer patients; this study is of great significance for revealing the mechanism of EBV infection inducing tumor cell metabolism reprogramming, and identifying neutral antibodies used to block INSL5 and receptor binding, which is of great significance to the personalized target treatment of nasopharyngeal cancer. it is known that Professor Zeng Musheng of Sun Yat-sen University Cancer Prevention and Control Center, Professor Yan Jianhua of Beijing Institute of Life Sciences, Professor Ling Zhiqiang of Zhejiang Cancer Hospital and Professor Zheng Yuming of the Luzhou Red Cross are co-authors of this paper, which is mainly done by Dr. Li Shibing, Dr. Liu Yanyan, Yuan Li Assistant Researcher and Professor Ji Mingfang. .