Snail blocks the cell cycle and confers resistance to cell death.
The Snail zinc-finger transcription factors trigger epithelial-mesenchymal transitions (EMTs), endowing epithelial cells with migratory and invasive properties during both embryonic development and tumor progression. During EMT, Snail provokes the loss of epithelial markers, as well as changes in cell shape and the expression of mesenchymal markers. Here, we show that in addition to inducing dramatic phenotypic alterations, Snail attenuates the cell cycle and confers resistance to cell death induced by the withdrawal of survival factors and by pro-apoptotic signals. Hence, Snail favors changes in cell shape versus cell division, indicating that with respect to oncogenesis, although a deregulation/increase in proliferation is crucial for tumor formation and growth, this may not be so for tumor malignization. Finally, the resistance to cell death conferred by Snail provides a selective advantage to embryonic cells to migrate and colonize distant territories, and to malignant cells to separate from the primary tumor, invade, and form metastasis.
Vega
Sonia
S
Instituto Cajal, Consejo Superior de Investigaciones Cieutificas, 28002 Madrid, Spain.
Morales
Aixa V
AV
Ocaña
Oscar H
OH
Valdés
Francisco
F
Fabregat
Isabel
I
Nieto
M Angela
MA
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002642:Chick Embryo; D016895:Culture Media, Serum-Free; D019938:Cyclin D1 / Q000235:genetics; D056742:Cyclin D2; D016213:Cyclins / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004285:Dogs; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C080336:CCND2 protein, human; C486196:Ccnd2 protein, mouse; D016895:Culture Media, Serum-Free; D056742:Cyclin D2; D016213:Cyclins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D019938:Cyclin D1