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PMID: 28427223 Published · ppublish English Journal Article

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

Oncotarget ·Vol. 8 ·No. 18 ·2017-05-02 ·Pages 30344-30356

Li Y, Jin L, Ye F, Ma Q, Yang Z, Liu D, Yang J, Ma D, Gao Q

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.

Keywords
E-Cadherin complex EphA10 EphA10s breast cancer lymphnode metastasis
MeSH Terms
Animals Breast Neoplasms/genetics,metabolism,mortality,pathology Cadherins/metabolism Cell Line, Tumor Cell Membrane/metabolism Cell Movement/genetics Disease Models, Animal Disease Progression Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Heterografts Humans Mice Neoplasm Metastasis Neoplasm Staging Phosphorylation Prognosis Protein Binding Protein Isoforms Protein Stability Protein Transport ROC Curve Receptors, Eph Family/genetics beta Catenin/metabolism
Chemicals
Cadherins Protein Isoforms beta Catenin EPHA10 protein, human Receptors, Eph Family
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Li Ye
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. | Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
Jin Lu
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
Ye Fei
Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Ma Quanfu
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Yang Zongyuan
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Liu Dan
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Yang Jie
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Ma Ding
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Gao Qinglei
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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Article Info
Journal
Oncotarget
Abbr.
Oncotarget
ISSN
1949-2553
DOI
10.18632/oncotarget.15910
Published
2017-05-02
Pages
30344-30356
Language
English
Region
United States
NLM ID
101532965
PMCID
PMC5444747
Subset
IM
External Links
PubMed source DOI: 10.18632/oncotarget.15910 PMC Full Text View journal details
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