Slug is required for cell survival during partial epithelial-mesenchymal transition of HGF-induced tubulogenesis.
Transcription factors of the Snail family are key regulators of epithelial-mesenchymal transition (EMT). In many processes during development or disease, cells do not acquire all the characteristics associated with EMT, leading to what we refer to as partial EMT (p-EMT). However, little is known of the implications of the Snail transcription factors in processes that only involve a p-EMT. To assess this, we used the hepatocyte growth factor (HGF)-induced Madin-Darby canine kidney tubulogenesis system, which provides a three-dimensional culture model of a morphogenetic process including a p-EMT. We found that although Slug (Snail2) is highly and transitory up-regulated during the p-EMT phase of tubulogenesis, it is not a repressor of E-cadherin during this process. Using inducible knockdown of Slug, we demonstrate that Slug is not an inducer of cell movement and instead is required for survival during p-EMT. We conclude that in epithelial cells, promoting cell survival can be a primary function of Slug, rather than being acquired concomitantly with EMT.
Leroy
Pascale
P
Department of Anatomy, University of California, San Francisco, CA 94158-2517, USA. pascal.leroy@ucsf.edu
Mostov
Keith E
KE
D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D004285:Dogs; D004848:Epithelium / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
D015820:Cadherins; D017931:DNA Primers; D012333:RNA, Messenger; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D017228:Hepatocyte Growth Factor