{"data":{"id":"10.6084/m9.figshare.1454520","type":"dois","attributes":{"doi":"10.6084/m9.figshare.1454520","prefix":"10.6084","suffix":"m9.figshare.1454520","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Ji, Runbi","givenName":"Runbi","familyName":"Ji","affiliation":[],"nameIdentifiers":[]},{"name":"Zhang, Bin","givenName":"Bin","familyName":"Zhang","affiliation":[],"nameIdentifiers":[]},{"name":"Zhang, Xu","givenName":"Xu","familyName":"Zhang","affiliation":[],"nameIdentifiers":[]},{"name":"Xue, Jianguo","givenName":"Jianguo","familyName":"Xue","affiliation":[],"nameIdentifiers":[]},{"name":"Yuan, Xiao","givenName":"Xiao","familyName":"Yuan","affiliation":[],"nameIdentifiers":[]},{"name":"Yan, Yongmin","givenName":"Yongmin","familyName":"Yan","affiliation":[],"nameIdentifiers":[]},{"name":"Wang, Mei","givenName":"Mei","familyName":"Wang","affiliation":[],"nameIdentifiers":[]},{"name":"Zhu, Wei","givenName":"Wei","familyName":"Zhu","affiliation":[],"nameIdentifiers":[]},{"name":"Qian, Hui","givenName":"Hui","familyName":"Qian","affiliation":[],"nameIdentifiers":[]},{"name":"Xu, Wenrong","givenName":"Wenrong","familyName":"Xu","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Exosomes derived from human mesenchymal stem cells confer drug resistance in gastric cancer"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2015,"subjects":[{"subject":"Biophysics"},{"subject":"Biochemistry"},{"subject":"Medicine"},{"subject":"Cell Biology"},{"subject":"Genetics"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Molecular Biology"},{"subject":"Pharmacology"},{"subject":"Biotechnology"},{"subject":"Chemical Sciences not elsewhere classified"},{"subject":"Biological Sciences not elsewhere classified"},{"subject":"Developmental Biology"},{"subject":"Cancer"},{"subject":"Hematology"},{"subject":"Infectious Diseases"},{"subject":"FOS: Health sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"}],"contributors":[],"dates":[{"date":"2015-10-09","dateType":"Created"},{"date":"2023-06-02","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"Dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.1080/15384101.2015.1005530","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["15215752 Bytes"],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"Mesenchymal stem cells (MSCs) play an important role in chemoresistance. Exosomes have been reported to modify cellular phenotype and function by mediating cell-cell communication. In this study, we aimed to investigate whether exosomes derived from MSCs (MSC-exosomes) are involved in mediating the resistance to chemotherapy in gastric cancer and to explore the underlying molecular mechanism. We found that MSC-exosomes significantly induced the resistance of gastric cancer cells to 5-fluorouracil both in vivo and ex vivo. MSC-exosomes antagonized 5-fluorouracil-induced apoptosis and enhanced the expression of multi-drug resistance associated proteins, including MDR, MRP and LRP. Mechanistically, MSC-exosomes triggered the activation of calcium/calmodulin-dependent protein kinases (CaM-Ks) and Raf/MEK/ERK kinase cascade in gastric cancer cells. Blocking the CaM-Ks/Raf/MEK/ERK pathway inhibited the promoting role of MSC-exosomes in chemoresistance. Collectively, MSC-exosomes could induce drug resistance in gastric cancer cells by activating CaM-Ks/Raf/MEK/ERK pathway. Our findings suggest that MSC-exosomes have profound effects on modifying gastric cancer cells in the development of drug resistance. Targeting the interaction between MSC-exosomes and cancer cells may help improve the efficacy of chemotherapy in gastric cancer.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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