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, Qinglei Gao

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 upregulated 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.

Original languageEnglish (US)
Pages (from-to)30344-30356
Number of pages13
JournalOncotarget
Volume8
Issue number18
DOIs
StatePublished - 2017
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the National Development Program (973) for Key Basic Research of China (grants 2009CB521800 and 2013CB911304), the National Science Foundation of China (grants 81072135, 81372801, 30901749 and 81272426).

Keywords

  • Breast cancer
  • E-Cadherin complex
  • EphA10
  • EphA10s
  • Lymphnode metastasis

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