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

Authors
 E Lee  ;  J Yang  ;  M Ku  ;  NH Kim  ;  Y Park  ;  CB Park  ;  J-S Suh  ;  ES Park  ;  JI Yook  ;  GB Mills  ;  Y-M Huh  ;  J-H Cheong 
Citation
 Cell Death & Disease, Vol.6 : 1805-1805, 2015 
Journal Title
 Cell Death & Disease 
ISSN
 2041-4889 
Issue Date
2015
Abstract
Reciprocal 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.
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DOI
10.1038/cddis.2015.171
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
Yonsei Authors
구민희(Ku, Min Hee) ORCID logo https://orcid.org/0000-0002-1674-1474
김남희(Kim, Nam Hee) ORCID logo https://orcid.org/0000-0002-3087-5276
박은성(Park, Eun Sung)
서진석(Suh, Jin Suck) ORCID logo https://orcid.org/0000-0001-9455-9240
양재문(Yang, Jae Moon) ORCID logo https://orcid.org/0000-0001-7365-0395
육종인(Yook, Jong In) ORCID logo https://orcid.org/0000-0002-7318-6112
이유진(Lee, Eu Gene)
정재호(Cheong, Jae Ho) ORCID logo https://orcid.org/0000-0002-1703-1781
허용민(Huh, Yong Min) ORCID logo https://orcid.org/0000-0002-9831-4475
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/140808
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