Oncotarget

Research Papers:

Isoform expression patterns of EPHA10 protein mediate breast cancer progression by regulating the E-Cadherin and β-catenin complex

Ye Li, Lu Jin, Fei Ye, Quanfu Ma, Zongyuan Yang, Dan Liu, Jie Yang, Ding Ma and Qinglei Gao _

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Oncotarget. 2017; 8:30344-30356. https://doi.org/10.18632/oncotarget.15910

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Abstract

Ye Li1,2, Lu Jin2, Fei Ye3, Quanfu Ma1, Zongyuan Yang1, Dan Liu1, Jie Yang1, Ding Ma1 and Qinglei Gao1

1Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

2Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA

3Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

Correspondence to:

Qinglei Gao, email: qlgao@tjh.tjmu.edu.cn

Keywords: EphA10s, EphA10, E-Cadherin complex, breast cancer, lymph node metastasis

Received: April 10, 2016    Accepted: February 07, 2017    Published: March 06, 2017

ABSTRACT

Overexpression of EPHA10 protein was reported in concomitance with clinical severity of breast cancer. In this study, we annotate overexpression of EPHA10 protein with changes of isoform expression as EphA10s (EPHA10 isoform 2) and EphA10 (EPHA10 isoform 3). In the process of malignant transformation, secretory protein EphA10s is in low expression, and pseudo-kinase EphA10 is overexpressed and cytoplasmically enriched. Down-regulated EphA10s blunts stabilization of membrane-associate β-catenin via the interaction with ephrin A5. Cytoplasmic EphA10 maintains phosphorylation of E-cadherin. Restoring isoform expression pattern by up-regulated EphA10s and down-regulated cytoplasmic EphA10 inhibits cell invasion and lymph node metastasis by strengthening the stability of the complex of E-cadherin and β-catenin in membrane. Taken together, we defined the novel interaction via expression patterns of EphA10s and EphA10 that promote malignant transformation of breast cancer, and demonstrated the potential benefit in clinical usage.


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