Ziyuglycoside II suppresses the aggressive phenotype of triple negative breast cancer cells through regulating Src/EGFR-dependent ITGB4/FAK signaling

Abstract

Triple negative breast cancer (TNBC), an aggressive form of breast cancer, has high rate of metastasis and which is the main cause of poor outcomes for such disease. The acquisition of invasive properties such as epithelial mesenchymal transition (EMT) and anoikis resistance is estimated to be the critical step in TNBC metastasis. Therefore, targeting these metastatic processes may contribute to the control of TNBC metastasis. In this study, investigations were conducted into the effect and mechanism of Ziyuglycoside II (Ziyu II), the main compound extracted from Sanguisorba Officinails L, on EMT, anoikis resistance as well as cell migration and invasion in human triple negative breast carcinoma MDA-MB-231 cells. The results showed that the treatment of Ziyu II could inhibit EMT, reverse anoikis resistance and subsequently suppress cell migration and invasion in MDA-MB-231 cells, which was associated with the inactivation of Src/EGFR-dependent ITGB4/FAK signaling and subsequent Akt and p38MAPK signaling pathways. These findings provide the new evidence of the anti-metastatic activity of Ziyu II and suggest the possibility of using this compound for the control of TNBC metastasis.

Keywords: Metastasis; Src/EGFR-dependent ITGB4/FAK signaling; Triple negative breast cancer; Ziyuglycoside II.