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AKR1B1 promotes pancreatic cancer metastasis by regulating lysosome-guided exosome secretion

Nano Research 2022年第6期15卷 5279-5294页

作者： Jie Ji Dandan Jin Minxue Xu Yujie Jiao Yue Wu Tong Wu Renjie Lin Wenjie Zheng Zhaoxiu Liu Feng Jiang Yihui Fan Mingbing Xiao Department of Gastroenterology Affiliated Hospital and Medical School of Nantong UniversityNantong 226001China Third People’s Hospital Affiliated to Nantong University Nantong 226001China Department of Gastroenterology Second People’s Hospital of ChangshuChangshu 215500China Research Center of Clinical Medicine Affiliated Hospital of Nantong UniversityNantong 226001China Department of Pathogenic Biology School of MedicineNantong UniversityNantong 226001China

Pancreatic cancer is one of the most lethal neoplasms with high metastatic potential and is resistant to almost all current *** is an aldo-keto reductase family 1 member B1(AKR1B1)inhibitor for the treatment of diabetic neuropathy,but its potential application in cancer treatment and the underlying mechanism are largely ***,we found that AKR1B1 is upregulated in pancreatic cancer and is positively associated with *** AKR1B1 promoted exosome secretion,accelerating cell migration in pancreatic cancer *** analysis indicated that AKR1B1 negatively regulated lysosomal function and multivesicular body(MVB)degradation in ***,AKR1B1 had a minimal role in the generation of *** factor EB(TFEB)and MVB-expressed RAB7A were two molecular targets that are negatively regulated by *** results uncovered a critical role for AKR1B1 in the regulation of lysosomal function and exosome *** targeting of AKR1B1 by clinically used medicines,such as Epalrestat,might represent an efficient way to inhibit pancreatic growth and metastasis.

关键词： aldo-keto reductase family 1 member B1(AKR1B1) pancreatic cancer exosome secretion lysosome Epalrestat

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The biogenesis and secretion of exosomes and multivesicular bodies(MVBs):Intercellular shuttles and implications in human diseases

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Genes & Diseases 2023年第5期10卷 1894-1907页

作者： Minxue Xu Jie Ji Dandan Jin Yue Wu Tong Wu Renjie Lin Shengze Zhu Feng Jiang Yifei Ji Baijun Bao Mei Li Weisong Xu Mingbing Xiao Department of Gastroenterology and Research Center of Clinical Medicine Affiliated Hospital and Medical School of Nantong UniversityNantongJiangsu 226001China Third People's Hospital Affiliated to Nantong University NantongJiangsu 226001China Medical School of Nantong University Oral Medcine192 NantongJiangsu 226001China Department of Medical Oncology Affiliated Hospital of Nantong UniversityNantongJiangsu 226001China Department of Gastroenterology Affiliated Nantong Rehabilitation Hospital of Nantong UniversityNantongJiangsu 226001China

exosomes carry and transmit signaling molecules used for intercellular *** generation and secretion of exosomes is a multistep interlocking process that allows simultaneous control of multiple regulatory *** molecules,mainly RAB GTPases,cytoskeletal proteins and soluble N-ethylmaleimide-sensitive fusion attachment protein receptor(SNARE),are specifically regulated in response to pathological conditions such as altered cellular microenvironment,stimulation by pathogenic factors,or gene *** interferes with the smooth functioning of endocytosis,translocation,degradation,docking and fusion processes,leading to changes in the secretion of *** numbers of secreted exosomes are disseminated by the flow of body fluids and absorbed by the recipient *** transmitting characteristic functional proteins and genetic information produced under disease conditions,exosomes can change the physiological state of the recipient cells and their *** microenvironment,in turn,affects the occurrence and development of ***,this review will discuss the mechanism by which exosome secretion is regulated in cells following the formation of mature secretory multivesicular bodies(MVBs).The overall aim is to find ways to eliminate disease-derived exosomes at their source,thereby providing an important new basis for the clinical treatment of disease.

关键词： Cellular microenvironment Cytoskeleton exosome secretion RAB GTPase SNARE

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