title: Sec8 modulates TGF-β induced EMT by controlling N-cadherin via regulation of Smad3/4.
abstract: Sec8 is one of the subunits of the exocyst, which is an evolutionarily conserved complex of eight proteins, comprising Sec3 (EXOC1), Sec5 (EXOC2), Sec6 (EXOC3), Sec8 (EXOC4), Sec10 (EXOC5), Sec15 (EXOC6), Exo70 (EXOC7), and Exo84 (EXOC8) subunits. Sec8 knockout mice embryos initiate gastrulation but are unable to progress beyond the primitive streak stage and die shortly. During embryonic development, the first epithelial-mesenchymal transition (EMT) event occurs at gastrulation. Sec8 may be involved in the early embryonic development through EMT. However, the function of Sec8 in EMT remains unclear. In the present study, it was found that Sec8 regulates N-cadherin expression by controlling Smad3 and Smad4 expression at the basal transcriptional level, thereby modulating cell migration and adhesion. Furthermore, Sec8 knockdown decreased CREB binding protein (CBP) expression at mRNA and protein levels. However, CBP knockdown did not affect Sec8 expression. These results indicated that Sec8 regulates N-cadherin expression by controlling Smad3 and Smad4 expression through CBP, thereby mediating the EMT.
authors: Department of Anatomy and Cell Biology, School of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Japan; Department of Dentistry, Oral and Maxillofacial Surgery, Plastic and Reconstructive Surgery, School of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Japan. Electronic address: ttanaka@med.id.yamagata-u.ac.jp.
authors: Toshiaki
authors: T
authors: Tanaka
authors: Department of Anatomy and Cell Biology, School of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Japan.
authors: Kaoru
authors: K
authors: Goto
authors: Department of Dentistry, Oral and Maxillofacial Surgery, Plastic and Reconstructive Surgery, School of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Japan.
authors: Mitsuyoshi
authors: M
authors: Iino
mesh_terms: D000072283:A549 Cells; D015703:Antigens, CD / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006657:Histones / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism; D051785:Smad Proteins / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; C489607:EXOC4 protein, human; D006657:Histones; D010446:Peptide Fragments; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D033921:Vesicular Transport Proteins; C571744:bone sialoprotein (35-62), human
keywords: CBP; EMT; N-cadherin; Sec8; Smad3; Smad4