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Baicalein Inhibits Epithelial to Mesenchymal Transition via Downregulation of Cyr61 and LOXL-2 in MDA-MB231 Breast Cancer Cells

  • Nguyen, Linh Thi Thao (Faculty of Biotechnology, College of Applied Life Sciences, SARI) ;
  • Song, Yeon Woo (Faculty of Biotechnology, College of Applied Life Sciences, SARI) ;
  • Cho, Somi Kim (Faculty of Biotechnology, College of Applied Life Sciences, SARI)
  • Received : 2016.10.18
  • Accepted : 2016.12.09
  • Published : 2016.12.31

Abstract

Epithelial-mesenchymal transition (EMT) is a critical step in the acquisition of the migratory and invasive capabilities associated with metastatic competence. Cysteine-rich protein 61 (CCN1/Cyr61) has been implicated as an important mediator in the proliferation and metastasis of breast cancer. Hence, Cyr61 and associated pathways are attractive targets for therapeutic interventions directed against the EMT. In the present study, we report that baicalein significantly inhibits the expression of Cyr61 and migration and invasion of MDA-MB231 human breast cancer cells. Exposure to baicalein led to increased E-cadherin expression, possibly due to the ubiquitination of Snail and Slug, which was mediated by the Cyr61/Akt/glycogen synthase kinase $3{\beta}$ ($GSK3{\beta}$) pathway. Further analysis revealed that baicalein inhibited the expression of lysyl oxidase like-2 (LOXL-2), which is a functional collaborator of Snail and Slug, and subsequently attenuated the direct interaction between LOXL-2 and Snail or Slug, thereby enhancing $GSK3{\beta}$-dependent Snail and Slug degradation. Our findings provide new insights into the antimetastatic mechanism of baicalein and may contribute to its beneficial use in breast cancer therapies.

Keywords

Baicalein;breast cancer;Cyr61;EMT;$GSK3{\beta}$;LOXL-2

Acknowledgement

Supported by : National Research Foundation of Korea(NRF), Ministry of Education

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