Caffeic acid phenethyl ester suppresses metastasis of breast cancer cells by inactivating FGFR1 via MD2

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Abstract
Background: Tumor metastasis is the main cause of death for breast cancer patients. Caffeic acid phenethyl ester (CAPE) has strong anti-tumor effects with very low toxicity and may be a potential candidate drug. However, the anti-metastatic effect and molecular mechanism of CAPE on breast cancer need more research. Methods: MCF-7 and MDA-MB-231 breast cancer cells were used here. Wound healing and Transwell assay were used for migration and invasion detection. Western blot and RT-qPCR were carried out for the epithelial-to-myofibroblast transformation (EMT) process investigation. Western blot and immunofluorescence were performed for fibroblast growth factor receptor1 (FGFR1) phosphorylation and nuclear transfer detection. Co-immunoprecipitation was used for the FGFR1/myeloid differentiation protein2 (MD2) complex investigation. Results: Our results suggested that CAPE blocks the migration, invasion, and EMT process of breast cancer cells. Mechanistically, CAPE inhibits FGFR1 phosphorylation and nuclear transfer while overexpression of FGFR1 reduces the anti-metastasis effect of CAPE. Further, we found that FGFR1 is bound to MD2, and silencing MD2 inhibits FGFR1 phosphorylation and nuclear transfer as well as cell migration and invasion. Conclusion: This study illustrated that CAPE restrained FGFR1 activation and nuclear transfer through MD2/FGFR1 complex inhibition and showed good inhibitory effects on the metastasis of breast cancer cells.
Funding Information
  • Wu Jieping Medical Foundation (320.6750.2021-10-26)
  • Medical Science and Technology Project of Zhejiang Province (2019KY037)
  • Natural Science Foundation of Zhejiang Province (LYY19H310002)
  • Medical Science and Technology Project of Zhejiang Province (2017190933)
  • Medical Science and Technology Project of Zhejiang Province (2018257156)

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