title: Baicalein Inhibits Epithelial to Mesenchymal Transition via Downregulation of Cyr61 and LOXL-2 in MDA-MB231 Breast Cancer Cells.
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 3β (GSK3β) 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 GSK3β-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.
authors.affiliation: Faculty of Biotechnology, College of Applied Life Sciences, SARI, Jeju National University, Jeju 63243, Korea.
authors.forename: Linh Thi Thao
authors.initials: LT
authors.lastname: Nguyen
authors.affiliation: Faculty of Biotechnology, College of Applied Life Sciences, SARI, Jeju National University, Jeju 63243, Korea.
authors.forename: Yeon Woo
authors.initials: YW
authors.lastname: Song
authors.affiliation: Faculty of Biotechnology, College of Applied Life Sciences, SARI, Jeju National University, Jeju 63243, Korea.|Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju 63243, Korea.
authors.forename: Somi Kim
authors.initials: SK
authors.lastname: Cho
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D015703:Antigens, CD; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D055515:Cysteine-Rich Protein 61 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D015703:Antigens, CD; C501848:CCN1 protein, human; C513384:CDH1 protein, human; D015820:Cadherins; D055515:Cysteine-Rich Protein 61; D044950:Flavanones; C006680:baicalein; D000594:Amino Acid Oxidoreductases; C119091:LOXL2 protein, human
keywords: Baicalein; Cyr61; EMT; GSK3β; LOXL-2; breast cancer