Journal
CANCER SCIENCE
Volume 112, Issue 3, Pages 1060-1074Publisher
WILEY
DOI: 10.1111/cas.14778
Keywords
EIF4E; ESCC; metastasis; MTA2; Twist
Categories
Funding
- Financial Department of Hebei province [20201067]
- Natural Science Foundation of Hebei Province [H2019206697]
- National Natural Science Foundation of China [81673642, 81772550]
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MTA2 is highly expressed in ESCC and significantly promotes ESCC growth and metastasis through a novel EIF4E-Twist positive feedback loop, which regulates the expression of E-cadherin and promotes aggressive progression of ESCC.
Metastasis-associated protein 2 (MTA2) is frequently amplified in many types of cancers; however, the role and underlying molecular mechanism of MTA2 in esophageal squamous cell carcinoma (ESCC) remain unknown. Here, we reported that MTA2 is highly expressed in ESCC tissue and cells, and is closely related to the malignant characteristics and poor prognosis of patients with ESCC. Through in vitro and in vivo experiments, we demonstrated that MTA2 significantly promoted ESCC growth, metastasis, and epithelial-mesenchymal transition (EMT) progression. This integrative analysis combined with expression microarray showed that MTA2 could interact with eukaryotic initiation factor 4E (EIF4E), which positively regulates the expression of Twist, known as a master regulator of EMT. Moreover, the results of chromatin immunoprecipitation revealed that MTA2 was recruited to the E-cadherin promoter by Twist, which reduced the acetylation level of the promoter region and thus inhibited expression of E-cadherin, and subsequently promoted the aggressive progression of ESCC. Collectively, our study provided novel evidence that MTA2 plays an aggressive role in ESCC metastasis by a novel EIF4E-Twist positive feedback loop, which may provide a potential therapeutic target for the management of ESCC.
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