1. MTA1 promotes tumorigenesis and development of esophageal squamous cell carcinoma via activating the MEK/ERK/p90RSK signaling pathway.
- Author
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Nan P, Wang T, Li C, Li H, Wang J, Zhang J, Dou N, Zhan Q, Ma F, Wang H, and Qian H
- Subjects
- Animals, Apoptosis, Biomarkers, Tumor genetics, Cell Proliferation, Disease Models, Animal, Esophageal Neoplasms genetics, Esophageal Neoplasms metabolism, Esophageal Squamous Cell Carcinoma genetics, Esophageal Squamous Cell Carcinoma metabolism, Gene Expression Regulation, Neoplastic, Humans, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Nude, Repressor Proteins genetics, Ribosomal Protein S6 Kinases, 90-kDa genetics, Signal Transduction, Trans-Activators genetics, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Biomarkers, Tumor metabolism, Esophageal Neoplasms pathology, Esophageal Squamous Cell Carcinoma pathology, MAP Kinase Signaling System, Repressor Proteins metabolism, Ribosomal Protein S6 Kinases, 90-kDa metabolism, Trans-Activators metabolism
- Abstract
Metastasis-associated protein 1 (MTA1) is upregulated in multiple malignancies and promotes cancer proliferation and metastasis, but whether and how MTA1 promotes esophageal squamous cell carcinoma (ESCC) tumorigenesis remain unanswered. Here, we established an ESCC model in MTA1 transgenic mice induced by the chemical carcinogen 4-nitroquinoline 1-oxide (4-NQO) and found that MTA1 promotes ESCC tumorigenesis in mice. MTA1 overexpression was observed in ESCC cells and clinical ESCC samples. Overexpressed MTA1 increased colony formation and the invasiveness and migration of ESCC cells, whereas knock down of MTA1 in ESCC cells significantly decreased colony formation, invasion and migration in vitro and inhibited the growth of xenograft tumors in vivo. RNA sequencing (RNA-seq) analysis combined with western blot assays revealed that MTA1 promotes carcinogenesis by enhancing MEK/ERK/p90RSK signaling. The phosphorylation of MEK, ERK and their downstream target p90RSK was significantly decreased after MTA1 knockdown in ESCC cells and was increased in MTA1-overexpressing cells. Moreover, colony formation, invasion and migration potential were dramatically suppressed when cells overexpressing MTA1 were treated with MEK (PD0325901) or ERK (SCH772948) inhibitors. In conclusion, MTA1 plays a pivotal oncogenic role in ESCC tumorigenesis and development through activating the MEK/ERK/p90RSK pathway., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2020
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