MTA1 promotes tumorigenesis and development of esophageal squamous cell carcinoma via activating the MEK/ERK/p90RSK signaling pathway

Author:

Nan Peng1,Wang Ting1,Li Chunxiao1,Li Hui1,Wang Jinsong1,Zhang Jingyao1,Dou Na1,Zhan Qimin2,Ma Fei3,Wang Haijuan1,Qian Haili1

Affiliation:

1. National Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital and Institute, Beijing, China

3. Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Abstract

AbstractMetastasis-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.

Funder

National Basic Research Program of China

CAMS Innovation Fund for Medical Sciences

National Natural Science Foundation of China

Open Issue of State Key Laboratory of Molecular Oncology

Independent Issue of State Key Laboratory of Molecular Oncology

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,General Medicine

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