A novel biphenyl urea derivate inhibits the invasion of breast cancer through the modulation of CXCR4

Journal of Cellular and Molecular Medicine
Yingzhuan ZhanLangchong He

Abstract

The increased migration and invasion of breast carcinoma cells are key events in the development of metastasis to the lymph nodes and distant organs. CXCR4, the receptor for stromal-derived factor-1, is reportedly involved in breast carcinogenesis and invasion. In this study, we investigated a novel biphenyl urea derivate, TPD7 for its ability to affect CXCR4 expression as well as function in breast cancer cells. We demonstrated that TPD7 inhibited the breast cancer proliferation and down-regulated the CXCR4 expression on breast cancer cells both over-expressing and low-expressing HER2, an oncogene known to induce the chemokine receptor. Treatments with pharmacological proteasome inhibitors partial suppressed TPD7-induced decrease in CXCR4 expression. Real-time PCR analysis revealed that down-regulation of CXCR4 by TPD7 also occurred at the translational level. Inhibition of CXCR4 expression by TPD7 further correlated with the suppression of SDF-1α-induced migration and invasion in breast tumour cells, knockdown of CXCR4 attenuated TPD7-inhibitory effects. In addition, TPD7 treatment significantly suppressed matrix metalloproteinase (MMP)-2 and MMP-9 expression, the downstream targets of CXCR4, perhaps via inactivation of the E...Continue Reading

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Citations

Jun 3, 2016·Journal of Veterinary Internal Medicine·M L ByrumT M Fan
Jul 28, 2016·Expert Opinion on Therapeutic Patents·Yung-Fong TsaiTsong-Long Hwang
Feb 12, 2017·BMC Bioinformatics·Claudia CavaIsabella Castiglioni

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Methods Mentioned

BETA
dissection
PCR
ubiquitination

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