title: Stem-like cancer cells are inducible by increasing genomic instability in cancer cells.
abstract: The 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: CSCs are 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, we found that DNA damage inducers, UV and mitomycin C were capable of increasing SP cells in NPC CNE-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.
authors.affiliation: State Key Laboratory of Oncology in Southern China, Guangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liang
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Zhong
authors.forename: Yijun
authors.initials: Y
authors.lastname: Huang
authors.forename: Wen
authors.initials: W
authors.lastname: Deng
authors.forename: Junxia
authors.initials: J
authors.lastname: Cao
authors.forename: George
authors.initials: G
authors.lastname: Tsao
authors.forename: Quentin
authors.initials: Q
authors.lastname: Liu
authors.forename: Duanqing
authors.initials: D
authors.lastname: Pei
authors.forename: Tiebang
authors.initials: T
authors.lastname: Kang
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
mesh_terms: D000071916:AC133 Antigen; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D064107:Aurora Kinase B; D064127:Aurora Kinases; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D005434:Flow Cytometry; D042822:Genomic Instability / Q000235:genetics / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007621:Karyotyping; D064246:Mad2 Proteins; D016685:Mitomycin / Q000633:toxicity; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: C116614:ABCG2 protein, human; D000071916:AC133 Antigen; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D006023:Glycoproteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D009363:Neoplasm Proteins; C000606023:PROM1 protein, human; D010455:Peptides; D012097:Repressor Proteins; D016685:Mitomycin; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases