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. 2021 Jan 15;22(2):849. doi: 10.3390/ijms22020849

Figure 5.

Figure 5

Role of Notch signaling in EMT caused by doxorubicin-induced tumor cells senescence. A proposed working model of Notch signals involved in breast cancer EMT in the co-cultivation system of senescent breast cancer cells induced by doxorubicin co-cultured with adjacent non-senescent breast cancer cells. Interactions between senescent (SEN-MCF-7) and adjacent non-senescent breast cancer cells (MCF-7-mRFP) through activating the Notch signal promote EMT of adjacent non-senescent breast cancer cells (MCF-7-mRFP) through Notch signaling, accompanied by the downregulation of E-cadherin and upregulation of Vimentin. Meanwhile, senescent breast cancer cells (SEN-MCF-7) return to the cell cycle and acquire migration and invasion ability and EMT properties, which is accompanied by the downregulation of E-cadherin and upregulation of Vimentin. Notch signaling in senescent (SEN-MCF-7) and adjacent non-senescent breast cancer cells (MCF-7-mRFP) is inhibited by treatment with DAPT in the co-cultivation system, which is accompanied by the downregulation of E-cadherin and upregulation of Vimentin in breast cancer cells. Red arrows: inhibition of signaling or downregulation of protein expression. Green arrows: activation of signaling or upregulation of protein expression.