title: SNAIL induces epithelial-to-mesenchymal transition and cancer stem cell-like properties in aldehyde dehydroghenase-negative thyroid cancer cells.
abstract: BACKGROUND
  Epithelial-to-mesenchymal transition (EMT) is thought to play a critical role in the invasion and metastasis of cancer and to be associated with cancer stem cell (CSC) properties. It is not clear if there is a link between EMT and CSCs in thyroid cancers. We therefore investigated the CSC properties of thyroid cancers that underwent EMT.
  
  
  METHODS
  To induce EMT (spindle-like cell morphology, loss and acquisition of expression of an epithelial marker E-cadherin and a mesenchymal marker vimentin respectively) in an epithelial-type thyroid cancer cell line ACT-1, we used transforming growth factor-β (TGF-β), BRAF(V600E), and/or Snail homolog 1 (SNAI1, also known as SNAIL). CSC properties were analyzed with assays for cell proliferation, chemosensitivity, in vitro and in vivo tumor formation ability, cell surface antigens, and intracellular aldehyde dehydrogenase (ALDH; a known CSC marker) activities.
  
  
  RESULTS
  EMT was induced most efficiently by SNAIL (ACT-SNAIL cells), whereas TGF-β and BRAF(V600E) were less efficient. ACT-SNAIL cells showed slightly but significantly enhanced tumor formation ability in an in vitro sphere assay (approximately 3-fold) but not an in vivo subcutaneous tumor growth assay, and showed comparable chemosensitivity compared with the parental ACT-1 cells. However, of interest, although the in vitro sphere-formation ability of ALDH(+) cells was almost unchanged after SNAIL induction, SNAIL overexpression induced much higher (approximately 14-fold) spheres in ALDH(-) cells. Thus, ALDH was no longer a CSC marker in ACT-SNAIL cells.
  
  
  CONCLUSIONS
  All these data indicate that EMT confers CSC properties in ALDH(-) cells and appears to influence the ability of ALDH to enrich CSCs.
authors: Department of Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors: Kazuaki
authors: K
authors: Yasui
authors: Mika
authors: M
authors: Shimamura
authors: Norisato
authors: N
authors: Mitsutake
authors: Yuji
authors: Y
authors: Nagayama
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000172:deficiency; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000473:pathology*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D000071250:Snail Family Transcription Factors; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*; D014157:Transcription Factors / Q000502:physiology*; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics; D014746:Vimentin / Q000378:metabolism
chemical_list: D015820:Cadherins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D014746:Vimentin; D000444:Aldehyde Dehydrogenase; D048493:Proto-Oncogene Proteins B-raf