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Integrated proteomic profiling identifies amino acids selectively cytotoxic to pancreatic cancer cells

The Innovation 2024年第3期5卷 138-145页

作者： Alfred Akinlalu Zachariah Flaten Komila Rasuleva Md Saimon Mia aaron bauer.santhalingam elamurugan Nega Ejjigu Sudipa Maity Amara Arshad Min Wu Wenjie Xia Jia Fan Ang Guo Sijo Mathew Dali Sun Department of Electrical and Computer Engineering University of Denver2155 E Wesley AvenueDenverCO 80210USA Biomedical Engineering Program North Dakota State University1401 Centennial BoulevardEngineering AdministrationRoom 203FargoND 58102USA Department of Pharmaceutical Sciences School of PharmacyNorth Dakota State University1001 S.1401 Albrecht Boulevard Sudro HallFargoND 58102USA Materials and Nanotechnology Program North Dakota State University1410 North 14th AvenueCIE 201FargoND 58102USA Wenzhou Institute University of Chinese Academy of SciencesWenzhouZhejiang 325000China Department of Aerospace Engineering Iowa State UniversityAmesIA 50011USA Center for Cellular and Molecular Diagnostics Tulane University School of Medicine1430 Tulane AvenueNew OrleansLA 70112USA Department of Biochemistry and Molecular Biology Tulane University School of Medicine1430 Tulane AvenueNew OrleansLA 70112USA Knoebel Institute for Healthy Aging University of Denver2155 E Wesley AvenueDenverCO 80210USA

Pancreatic adenocarcinoma(PDAC)is one of the most deadly cancers,characterized by extremely limited therapeutic options and a poor prognosis,as it is often diagnosed during late disease *** and selective treatments are urgently needed,since current therapies have limited efficacy and significant side *** proteomics analysis of extracellular vesicles,we discovered an imbalanced distribution of amino acids secreted by PDAC tumor *** findings revealed that PDAC cells preferentially excrete proteins with certain preferential amino acids,including isoleucine and histidine,via extracellular *** amino acids are associated with disease progression and can be targeted to elicit selective toxicity to PDAC tumor *** in vitro and in vivo experiments demonstrated that supplementation with these specific amino acids effectively eradicated PDAC ***,we also identified XRN1 as a potential target for these amino *** high selectivity of this treatment method allows for specific targeting of tumor metabolism with very low toxicity to normal ***,we found this treatment approach is easy-to-administer and with sustained tumor-killing ***,our findings reveal that exocytosed amino acids may serve as therapeutic targets for designing treatments of intractable PDAC and potentially offer alternative treatments for other types of cancers.

关键词： finding identif selectivity

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