MTA1 promotes tumorigenesis and development of esophageal squamous cell carcinoma via activating the MEK/ERK/p90RSK signaling pathway
| Autor: | Fei Ma, Ting Wang, Qimin Zhan, Haili Qian, Hui Li, Peng Nan, Haijuan Wang, Jinsong Wang, Na Dou, Jingyao Zhang, Chunxiao Li |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
MAPK/ERK pathway Cancer Research Esophageal Neoplasms MAP Kinase Signaling System Mice Nude Apoptosis medicine.disease_cause Ribosomal Protein S6 Kinases 90-kDa Mice Downregulation and upregulation Biomarkers Tumor Tumor Cells Cultured medicine Animals Humans neoplasms Cell Proliferation Mice Inbred BALB C Gene knockdown Cell growth Chemistry General Medicine Xenograft Model Antitumor Assays digestive system diseases Gene Expression Regulation Neoplastic Mice Inbred C57BL Repressor Proteins Disease Models Animal Cell culture Trans-Activators Cancer research Esophageal Squamous Cell Carcinoma Signal transduction Carcinogenesis Signal Transduction |
| Zdroj: | Carcinogenesis. 41:1263-1272 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgz200 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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