RRC ID 38353
Author Asanoma K, Liu G, Yamane T, Miyanari Y, Takao T, Yagi H, Ohgami T, Ichinoe A, Sonoda K, Wake N, Kato K.
Title Regulation of the Mechanism of TWIST1 Transcription by BHLHE40 and BHLHE41 in Cancer Cells.
Journal Mol. Cell. Biol.
Abstract BHLHE40 and BHLHE41 (BHLHE40/41) are basic helix-loop-helix type transcription factors that play key roles in multiple cell behaviors. BHLHE40/41 were recently shown to be involved in an epithelial-to-mesenchymal transition (EMT). However, the precise mechanism of EMT control by BHLHE40/41 remains unclear. In the present study, we demonstrated that BHLHE40/41 expression was controlled in a pathological stage-dependent manner in human endometrial cancer (HEC). Our in vitro assays showed that BHLHE40/41 suppressed tumor cell invasion. BHLHE40/41 also suppressed the transcription of the EMT effectors SNAI1, SNAI2, and TWIST1. We identified the critical promoter regions of TWIST1 for its basal transcriptional activity. We elucidated that the transcription factor SP1 was involved in the basal transcriptional activity of TWIST1 and that BHLHE40/41 competed with SP1 for DNA binding to regulate gene transcription. This study is the first to report the detailed functions of BHLHE40 and BHLHE41 in the suppression of EMT effectors in vitro. Our results suggest that BHLHE40/41 suppress tumor cell invasion by inhibiting EMT in tumor cells. We propose that BHLHE40/41 are promising markers to predict the aggressiveness of each HEC case and that molecular targeting strategies involving BHLHE40/41 and SP1 may effectively regulate HEC progression.
Volume 35(24)
Pages 4096-109
Published 2015-12
DOI 10.1128/MCB.00678-15
PII MCB.00678-15
PMID 26391953
PMC PMC4648814
MeSH Basic Helix-Loop-Helix Transcription Factors / biosynthesis Basic Helix-Loop-Helix Transcription Factors / genetics* Binding Sites / genetics Biomarkers, Tumor / genetics Cell Line, Tumor DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Disease Progression Endometrial Neoplasms / genetics* Endometrial Neoplasms / pathology Epithelial-Mesenchymal Transition / genetics Female HEK293 Cells Homeodomain Proteins / biosynthesis Homeodomain Proteins / genetics* Humans Neoplasm Invasiveness / genetics Neoplasm Invasiveness / pathology Nuclear Proteins / genetics* Promoter Regions, Genetic / genetics RNA Interference RNA, Messenger / genetics RNA, Small Interfering Snail Family Transcription Factors Sp1 Transcription Factor / genetics* Transcription Factors / genetics Transcription, Genetic / genetics Twist-Related Protein 1 / genetics*
IF 3.735
Times Cited 3
Human and Animal Cells HHUA(RCB0658)