Neural regulation of pancreatic cancer and islet function

This presentation explores the neural regulation of pancreatic cancer and pancreatic islet function within a systemic framework centered on interactions among the nervous, endocrine, and immune systems. It first highlights the diverse roles of serotonin (5-HT) in tumor biology. In addition to receptor-mediated signaling, 5-HT regulates antitumor immunity and the tumor microenvironment through TGM2-dependent serotonylation. Serotonylation of GAPDH promotes glycolytic metabolism and effector function in CD8⁺ T cells, whereas serotonylation of LOX enhances extracellular matrix crosslinking and stiffness, thereby facilitating pancreatic cancer progression.

Whole-pancreas tissue clearing and three-dimensional imaging further reveal an organized spatial relationship between sympathetic nerves and pancreatic islets. Rather than being passively innervated, islets actively attract, organize, and maintain sympathetic axons. Transplantation, denervation, and islet-ablation experiments demonstrate that this bidirectional interaction is largely mediated by islet-derived Reg family proteins, particularly Reg2 and Reg3b. These findings provide new insights into neuroendocrine communication and suggest potential therapeutic strategies for pancreatic cancer and diabetes.

Deputy Director of Shanghai Cancer Institute, and Principal Investigator of the Neurotransmitters and Tumor Microenvironment Research Team at the State Key Laboratory of Systems Medicine for Cancer. Former Chairman of the Matrix Biology Committee of the Chinese Physiological Society.

He has received research grants from key programs of the National Natural Science Foundation of China (NSFC), NSFC Original Exploration Program, NSFC Major Research Plan, the National Major Science and Technology Project of China during the 12th FiveYear Plan, and the National Hightech Research and Development Program of China (863 Program), among others.

He serves as Executive EditorinChief of Translational Research and Editorial Board Member of Chemistry of Life. As the corresponding author, he has published numerous papers in internationally renowned journals including Molecular Cell, Neuron, Gastroenterology, Gut, Nature Communications, Hepatology, Journal of Hepatology, American Journal of Gastroenterology, Genome Biology, Molecular Therapy, Clinical Cancer Research, Cancer Research, and Oncogene.

He is a recipient of honors including Shanghai Leading Talent, Shanghai Outstanding Academic Leader, Outstanding Academic Leader of Shanghai Municipal Health System, and the PlateauPeak Program of Shanghai Jiao Tong University School of Medicine.

He has filed 9 Chinese national invention patents, obtained 6 authorized Chinese national patents and 1 authorized international PCT patent. He has participated in compiling 2 monographs in Chinese and English. He was the first completer for the Second Prize of Shanghai Medical Science and Technology Award.