407 462

Cited 18 times in

Metabolic stress induces a Wnt-dependent cancer stem cell-like state transition

DC FieldValueLanguage
dc.contributor.author이유진-
dc.contributor.author정재호-
dc.contributor.author허용민-
dc.contributor.author구민희-
dc.contributor.author김남희-
dc.contributor.author박은성-
dc.contributor.author서진석-
dc.contributor.author양재문-
dc.contributor.author육종인-
dc.date.accessioned2016-02-04T11:36:42Z-
dc.date.available2016-02-04T11:36:42Z-
dc.date.issued2015-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/140808-
dc.description.abstractReciprocal interactions between cancer cells and the tumor microenvironment drive multiple clinically significant behaviors including dormancy, invasion, and metastasis as well as therapy resistance. These microenvironment-dependent phenotypes share typical characteristics with cancer stem cells (CSC). However, it is poorly understood how metabolic stress in the confined tumor microenvironment contributes to the emergence and maintenance of CSC-like phenotypes. Here, we demonstrate that chronic metabolic stress (CMS) in a long-term nutrient deprivation induces a Wnt-dependent phenoconversion of non-stem cancer cells toward stem-like state and this is reflected in the transcriptome analysis. Addition of Wnt3a as well as transfection of dominant-negative Tcf4 establishes an obligatory role for the Wnt pathway in the acquisition of CSC-like characteristics in response to metabolic stress. Furthermore, systematic characterization for multiple single cell-derived clones and negative enrichment of CD44+/ESA+ stem-like cancer cells, all of which recapitulate stem-like cancer characteristics, suggest stochastic adaptation rather than selection of pre-existing subclones. Finally, CMS in the tumor microenvironment can drive a CSC-like phenoconversion of non-stem cancer cells through stochastic state transition dependent on the Wnt pathway. These findings contribute to an understanding of the metabolic stress-driven dynamic transition of non-stem cancer cells to a stem-like state in the tumor metabolic microenvironment.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.relation.isPartOfCELL DEATH & DISEASE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHBreast Neoplasms/pathology*-
dc.subject.MESHCell Proliferation-
dc.subject.MESHCell Survival-
dc.subject.MESHFemale-
dc.subject.MESHHumans-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred BALB C-
dc.subject.MESHMice, Nude-
dc.subject.MESHNeoplastic Stem Cells/cytology*-
dc.subject.MESHNeoplastic Stem Cells/pathology-
dc.subject.MESHSpheroids, Cellular/pathology-
dc.subject.MESHStress, Physiological/physiology*-
dc.subject.MESHTranscription, Genetic/genetics-
dc.subject.MESHTranscriptional Activation/genetics-
dc.subject.MESHTumor Cells, Cultured-
dc.subject.MESHTumor Microenvironment/physiology-
dc.subject.MESHWnt Signaling Pathway/physiology*-
dc.subject.MESHWnt3A Protein/metabolism*-
dc.subject.MESHXenograft Model Antitumor Assays-
dc.titleMetabolic stress induces a Wnt-dependent cancer stem cell-like state transition-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Surgery (외과학)-
dc.contributor.googleauthorE Lee-
dc.contributor.googleauthorJ Yang-
dc.contributor.googleauthorM Ku-
dc.contributor.googleauthorNH Kim-
dc.contributor.googleauthorY Park-
dc.contributor.googleauthorCB Park-
dc.contributor.googleauthorJ-S Suh-
dc.contributor.googleauthorES Park-
dc.contributor.googleauthorJI Yook-
dc.contributor.googleauthorGB Mills-
dc.contributor.googleauthorY-M Huh-
dc.contributor.googleauthorJ-H Cheong-
dc.identifier.doi10.1038/cddis.2015.171-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA03016-
dc.contributor.localIdA03717-
dc.contributor.localIdA04359-
dc.contributor.localIdA00191-
dc.contributor.localIdA00360-
dc.contributor.localIdA01609-
dc.contributor.localIdA01916-
dc.contributor.localIdA02536-
dc.contributor.localIdA02315-
dc.relation.journalcodeJ00482-
dc.identifier.eissn2041-4889-
dc.identifier.pmid26136078-
dc.contributor.alternativeNameLee, Eu Gene-
dc.contributor.alternativeNameCheong, Jae Ho-
dc.contributor.alternativeNameHuh, Yong Min-
dc.contributor.alternativeNameKu, Min Hee-
dc.contributor.alternativeNameKim, Nam Hee-
dc.contributor.alternativeNamePark, Eun Sung-
dc.contributor.alternativeNameSuh, Jin Suck-
dc.contributor.alternativeNameYang, Jae Moon-
dc.contributor.alternativeNameYook, Jong In-
dc.contributor.affiliatedAuthorLee, Eu Gene-
dc.contributor.affiliatedAuthorCheong, Jae Ho-
dc.contributor.affiliatedAuthorHuh, Yong Min-
dc.contributor.affiliatedAuthorKu, Min Hee-
dc.contributor.affiliatedAuthorKim, Nam Hee-
dc.contributor.affiliatedAuthorPark, Eun Sung-
dc.contributor.affiliatedAuthorSuh, Jin Suck-
dc.contributor.affiliatedAuthorYook, Jong In-
dc.contributor.affiliatedAuthorYang, Jae Moon-
dc.rights.accessRightsfree-
dc.citation.volume6-
dc.citation.startPage1805-
dc.identifier.bibliographicCitationCELL DEATH & DISEASE, Vol.6 : 1805, 2015-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Institute for Medical Convergence (연의-생공연 메디컬융합연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.