Article: Stem-like cancer cells are inducible by increasing genomic instability in cancer cells

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TitleStem-like cancer cells are inducible by increasing genomic instability in cancer cells
AuthorsLiang, Y1
Zhong, Z1
Huang, Y4
Deng, W2
Cao, J1
Tsao, G2
Liu, Q1
Pei, D3
Kang, T1
Zeng, YX1
Issue Date2010
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
CitationJournal Of Biological Chemistry, 2010, v. 285 n. 7, p. 4931-4940 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M109.048397
AbstractThe existence of cancer stem cells (CSCs) or stem-like cancer cells (SLCCs) is regarded as the cause of tumor formation and recurrence. However, the origin of such cells remains controversial with two competing hypotheses:CSCsare either transformed from tissue adult stem cells or dedifferentiated from transformed progenitor cells. Compelling evidence has determined the chromosomal aneuploidy to be one of the hallmarks of cancer cells, indicating genome instability plays an important role in tumorigenesis, for which CSCs are believed to be the initiator. To gain direct evidence that genomic instability is involved in the induction of SLCCs, we utilized multiple approaches to enhance genomic instability and monitored the percentage of SLCC in cultured cancer cells. Using side population (SP) cells as a marker for SLCC in human nasopharyngeal carcinoma (NPC) and CD133 for human neuroblastoma cells,wefound thatDNAdamageinducers,UVand mitomycin C were capable of increasing SP cells in NPCCNE-2 and neuroblastoma SKN-SH cells. Likewise, either overexpression of a key regulator of cell cycle, Mad2, or knock down of Aurora B, an important kinase in mitosis, or Cdh1, a key E3 ligase in cell cycle, resulted in a significant increase of SP cells in CNE-2. More interestingly, enrichment of SP cells was observed in recurrent tumor tissues as compared with the primary tumor in the same NPC patients. Our study thus suggested that, beside transformation of tissue stem cells leading to CSC generation, genomic instability could be another potential mechanism resulting in SLCC formation, especially at tumor recurrence stage. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
ISSN0021-9258
2011 Impact Factor: 4.773
2011 SCImago Journal Rankings: 0.793
DOIhttp://dx.doi.org/10.1074/jbc.M109.048397
ISI Accession Number IDWOS:000275274800070
Funding AgencyGrant Number
Chinese National 973 Program2006CB910104
2010CB912201
Chinese National 863 Program2006AA02A404
Guangdong Province-National Natural Science Foundation of Chinau0732005
Funding Information:

The work was supported by the Chinese National 973 Program (Grants 2006CB910104 and 2010CB912201), the Chinese National 863 Program (Grant 2006AA02A404), and the Guangdong Province-National Natural Science Foundation of China Cooperation Program (Grant u0732005).

PubMed Central IDPMC2836097
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorLiang, Y
dc.contributor.authorZhong, Z
dc.contributor.authorHuang, Y
dc.contributor.authorDeng, W
dc.contributor.authorCao, J
dc.contributor.authorTsao, G
dc.contributor.authorLiu, Q
dc.contributor.authorPei, D
dc.contributor.authorKang, T
dc.contributor.authorZeng, YX
dc.date.accessioned2010-10-31T10:36:26Z
dc.date.available2010-10-31T10:36:26Z
dc.date.issued2010
dc.description.abstractThe existence of cancer stem cells (CSCs) or stem-like cancer cells (SLCCs) is regarded as the cause of tumor formation and recurrence. However, the origin of such cells remains controversial with two competing hypotheses:CSCsare either transformed from tissue adult stem cells or dedifferentiated from transformed progenitor cells. Compelling evidence has determined the chromosomal aneuploidy to be one of the hallmarks of cancer cells, indicating genome instability plays an important role in tumorigenesis, for which CSCs are believed to be the initiator. To gain direct evidence that genomic instability is involved in the induction of SLCCs, we utilized multiple approaches to enhance genomic instability and monitored the percentage of SLCC in cultured cancer cells. Using side population (SP) cells as a marker for SLCC in human nasopharyngeal carcinoma (NPC) and CD133 for human neuroblastoma cells,wefound thatDNAdamageinducers,UVand mitomycin C were capable of increasing SP cells in NPCCNE-2 and neuroblastoma SKN-SH cells. Likewise, either overexpression of a key regulator of cell cycle, Mad2, or knock down of Aurora B, an important kinase in mitosis, or Cdh1, a key E3 ligase in cell cycle, resulted in a significant increase of SP cells in CNE-2. More interestingly, enrichment of SP cells was observed in recurrent tumor tissues as compared with the primary tumor in the same NPC patients. Our study thus suggested that, beside transformation of tissue stem cells leading to CSC generation, genomic instability could be another potential mechanism resulting in SLCC formation, especially at tumor recurrence stage. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
dc.description.naturelink_to_OA_fulltext
dc.identifier.citationJournal Of Biological Chemistry, 2010, v. 285 n. 7, p. 4931-4940 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M109.048397
dc.identifier.citeulike11284570
dc.identifier.doihttp://dx.doi.org/10.1074/jbc.M109.048397
dc.identifier.epage4940
dc.identifier.hkuros182598
dc.identifier.isiWOS:000275274800070
Funding AgencyGrant Number
Chinese National 973 Program2006CB910104
2010CB912201
Chinese National 863 Program2006AA02A404
Guangdong Province-National Natural Science Foundation of Chinau0732005
Funding Information:

The work was supported by the Chinese National 973 Program (Grants 2006CB910104 and 2010CB912201), the Chinese National 863 Program (Grant 2006AA02A404), and the Guangdong Province-National Natural Science Foundation of China Cooperation Program (Grant u0732005).

dc.identifier.issn0021-9258
2011 Impact Factor: 4.773
2011 SCImago Journal Rankings: 0.793
dc.identifier.issue7
dc.identifier.openurl
dc.identifier.pmcidPMC2836097
dc.identifier.pmid20007324
dc.identifier.scopuseid_2-s2.0-77951192102
dc.identifier.spage4931
dc.identifier.urihttp://hdl.handle.net/10722/124474
dc.identifier.volume285
dc.languageeng
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
dc.publisher.placeUnited States
dc.relation.ispartofJournal of Biological Chemistry
dc.relation.referencesReferences in Scopus
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.
dc.rightsThis research was originally published in [Journal Name]. Author(s). Title. Journal Name. Year. Vol:pp-pp. © the American Society for Biochemistry and Molecular Biology
dc.subject.meshATP-Binding Cassette Transporters - metabolism
dc.subject.meshAntigens, CD - metabolism
dc.subject.meshBlotting, Western
dc.subject.meshGenomic Instability - genetics - physiology
dc.subject.meshNeoplastic Stem Cells - cytology - metabolism
dc.titleStem-like cancer cells are inducible by increasing genomic instability in cancer cells
dc.typeArticle
Author Affiliations
  1. Sun Yat-Sen University Cancer Center
  2. The University of Hong Kong
  3. Guangzhou Institute of Biomedicine and Health
  4. Sun Yat-Sen University