title: Downregulation of transcription factor SOX2 in cancer stem cells suppresses growth and metastasis of lung cancer.
abstract: BACKGROUND
  The cancer stem cell hypothesis suggests that neoplastic clones are maintained exclusively by a small subpopulation of cells, which have indefinite proliferation and differentiation potentials and give rise to phenotypically diverse cancer cells. Cancer stem cells have been isolated by their ability to efflux Hoechst 33342 dye and are referred to as the 'side population' (SP).
  
  
  RESULTS
  The Hoechst efflux assay was used to isolate and characterize the SP from murine D121 lung carcinoma cells. Here, we demonstrated that D121-SP cells contain cancer stem cell characteristics, that is, upregulation of the transcription factors SOX2 and Oct 4 in D121-SP cells. In addition, the migration of D121-SP was decreased, and apoptosis of D121-SP was upregulated following knocking down of SOX2 in D121 cells. Importantly, downregulation of SOX2 in D121 cells markedly suppressed their metastatic potential in syngeneic mice.
  
  
  CONCLUSIONS
  These results suggest that the SP is an enriched source of lung tumour cells with stem cell properties and that SOX2 has an important role in maintaining stem cell properties and functions that may be a potential target for effective lung cancer therapy.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: R
authors.initials: R
authors.lastname: Xiang
authors.forename: D
authors.initials: D
authors.lastname: Liao
authors.forename: T
authors.initials: T
authors.lastname: Cheng
authors.forename: H
authors.initials: H
authors.lastname: Zhou
authors.forename: Q
authors.initials: Q
authors.lastname: Shi
authors.forename: T S
authors.initials: TS
authors.lastname: Chuang
authors.forename: D
authors.initials: D
authors.lastname: Markowitz
authors.forename: R A
authors.initials: RA
authors.lastname: Reisfeld
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
mesh_terms: D000818:Animals; D017209:Apoptosis; D001562:Benzimidazoles; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques / Q000379:methods; D020868:Gene Silencing; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D050814:Octamer Transcription Factor-3; D034741:RNA, Small Interfering; D051880:Receptors, Notch; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation; D051153:Wnt Proteins
chemical_list: D001562:Benzimidazoles; D005456:Fluorescent Dyes; D050814:Octamer Transcription Factor-3; D034741:RNA, Small Interfering; D051880:Receptors, Notch; D055748:SOXB1 Transcription Factors; D051153:Wnt Proteins; C017807:bisbenzimide ethoxide trihydrochloride