Adam9 functions as a transcriptional regulator to drive angiogenesis in esophageal squamous cell carcinoma
Journal
International Journal of Biological Sciences
Journal Volume
17
Journal Issue
14
Pages
3898-3910
Date Issued
2021
Author(s)
Lin Y.-S.
Kuo T.-T.
Lo C.-C.
Cheng W.-C.
Chang W.-C.
Tseng G.-C.
Bai S.-T.
Huang Y.-K.
Hsieh C.-Y.
Hsu H.-S.
Jiang Y.-F.
Lin C.-Y.
Li X.-G.
Abstract
metastasis in ESCC xenograft mouse models. Using cellular fractionation and imaging, we found a fraction of ADAM9 was present in the nucleus and was uniquely associated with gene loci known to be linked to the angiogenesis pathway demonstrated by genome-wide ChIP-seq. Mechanistically, nuclear ADAM9, triggered by hypoxia-induced translocation, functions as a transcriptional repressor by binding to promoters of genes involved in the negative regulation of angiogenesis, and thereby promotes tumor angiogenesis in plasminogen/plasmin pathway. Moreover, ADAM9 suppresses plasminogen activator inhibitor-1 gene transcription by interacting with its transcription factors at the promoter. Our findings uncover a novel regulatory mechanism of ADAM9 as a transcriptional regulator in angiogenesis and highlight ADAM9 as a promising therapeutic target for ESCC treatment.
Publisher
Ivyspring International Publisher
Type
journal article