Open AccessProtein Kinase C-Induced Early Growth Response Protein-1 Binding to SNAIL Promoter in Epithelial–Mesenchymal Transition of Human Embryonic Stem Cells
Author(s) -
Masaki Kinehara,
Suguru Kawamura,
Sumiyo Mimura,
Mika Suga,
Akiko Hamada,
Mari Wakabayashi,
Hiroki Nikawa,
Miho Furue
Publication year - 2014
Publication title -
stem cells and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 114
eISSN - 1557-8534
pISSN - 1547-3287
DOI - 10.1089/scd.2013.0424
Subject(s) - biology , microbiology and biotechnology , protein kinase b , ectopic expression , embryonic stem cell , cellular differentiation , protein kinase a , signal transduction , epithelial–mesenchymal transition , stem cell , fibroblast growth factor , kinase , downregulation and upregulation , cell culture , genetics , gene , receptor
Epithelial-mesenchymal transition (EMT) has been thought to occur during early embryogenesis, and also the differentiation process of human embryonic stem (hES) cells. Spontaneous differentiation is sometimes observed at the peripheral of the hES cell colonies in conventional culture conditions, indicating that EMT occurs in hES cell culture. However, the triggering mechanism of EMT is not yet fully understood. The balance between self-renewal and differentiation of human pluripotent stem (hPS) cells is controlled by various signal pathways, including the fibroblast growth factor (FGF)-2. However, FGF-2 has a complex role for self-renewal of hES cells. FGF-2 activates phosphatidylinositol-3 kinase/AKT, mitogen-activated protein kinase/extracellular signal-regulated kinase-1/2 kinase, and also protein kinase C (PKC). Here, we showed that a PKC rapidly induced an early growth response protein-1 (EGR-1) in hES cells, which was followed by upregulation of EMT-related genes. Before the induction of EMT-related genes, EGR-1 was translocated into the nucleus, and then bound directly to the promoter region of SNAIL, which is a master regulator of EMT. SNAIL expression was attenuated by knockdown of EGR-1, but upregulated by ectopic expression of EGR-1. EGR-1 as the downstream signal of PKC might play a key role in EMT initiation during early differentiation of hES cells. This study would lead to a more robust understanding of the mechanisms underlying the balance between self-renewal and initiation of differentiation in hPS cells.