Ehm2 transcript variant 1 inhibits breast cancer progression and increases E-cadherin stability

Author:

Yin Xin1,Li Gen1,Fan Dongwei2,Ge Zhicheng3,Yang Tianshu1,Shang Yaxin1,Ma Tianyu4,Yuan Baowen4,Huang Wei1,Teng Xu1,Yu Hefen1ORCID

Affiliation:

1. Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University , Beijing 100069 , China

2. Department of Orthopaedics, Peking University Third Hospital , Beijing 100191 , China

3. Department of General Surgery, Beijing Friendship Hospital, Capital Medical University , Beijing 100050 , China

4. Key Laboratory of Cancer and Microbiome, State 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 100021 , China

Abstract

Abstract Ehm2/1, an Ehm2 transcript variant, regulates the cytoskeleton by binding to plasma membrane proteins. However, the role of Ehm2/1 in breast cancer development remains poorly understood. This study shows that, the expression of Ehm2/1 was decreased in breast cancer and that patients with low Ehm2/1 expression had a significantly poorer prognosis than those with high expression of Ehm2/1. Overexpression of Ehm2/1 in MCF-7 breast cancer cells inhibited cell migration and invasion. Ehm2/1 markedly increased the stability and half-life of E-cadherin. Moreover, Ehm2/1 was collocated with E-cadherin in the plasma membrane of MCF-7 cells. Furthermore, downregulation of Ehm2/1 promoted ubiquitination of E-cadherin, whereas overexpression of Ehm2/1 inhibited ubiquitination of E-cadherin. These results suggest that Ehm2/1 could suppress the migration and invasion of breast cancer cells by increasing E-cadherin stability.

Funder

National Natural Science Foundation of China

State Key Laboratory of Molecular Oncology

Natural Science Foundation of Beijing Municipality

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,General Medicine

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