{"title":"Oncogenic KRAS Promotes Ferroptosis in Pancreatic Cancer through Regulation of the FOSL1-TFRC Axis.","authors":"Huijia Zhao, Qi Huang, Yingao Liu, Wenming Wu","doi":"10.1097/MPA.0000000000002426","DOIUrl":null,"url":null,"abstract":"<p><strong>Abstract: </strong>Mutant KRAS activation occurs in most of pancreatic cancer (PDAC) which induce the sensitivity to ferroptosis of PDAC cells, but the underlying mechanism is still poorly understood. Here, we show how KRAS acts in signaling to activate transcription factor FOSL1, which promotes the expression of the iron uptake receptor TFRC. In PDAC cells, repression of TFRC by KRAS/FOSL1 signaling inhibited intracellular iron levels, thereby restricting the occurrence of ferroptosis. Furthermore, the KRAS/FOSL1/TFRC axis can make the PDAC cells vulnerable to alteration of the iron level in the tumor microenvironment. Our study highlights a pivotal mechanism of PDAC ferroptosis through iron metabolism and supports a new therapeutic strategy for PDAC with superior potential.</p>","PeriodicalId":19733,"journal":{"name":"Pancreas","volume":" ","pages":""},"PeriodicalIF":1.7000,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pancreas","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/MPA.0000000000002426","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Abstract: Mutant KRAS activation occurs in most of pancreatic cancer (PDAC) which induce the sensitivity to ferroptosis of PDAC cells, but the underlying mechanism is still poorly understood. Here, we show how KRAS acts in signaling to activate transcription factor FOSL1, which promotes the expression of the iron uptake receptor TFRC. In PDAC cells, repression of TFRC by KRAS/FOSL1 signaling inhibited intracellular iron levels, thereby restricting the occurrence of ferroptosis. Furthermore, the KRAS/FOSL1/TFRC axis can make the PDAC cells vulnerable to alteration of the iron level in the tumor microenvironment. Our study highlights a pivotal mechanism of PDAC ferroptosis through iron metabolism and supports a new therapeutic strategy for PDAC with superior potential.
期刊介绍：
Pancreas provides a central forum for communication of original works involving both basic and clinical research on the exocrine and endocrine pancreas and their interrelationships and consequences in disease states. This multidisciplinary, international journal covers the whole spectrum of basic sciences, etiology, prevention, pathophysiology, diagnosis, and surgical and medical management of pancreatic diseases, including cancer.
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