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. 2016 Jun 16;11(6):e0157397. doi: 10.1371/journal.pone.0157397

Fig 6. Dasatinib promotes nuclear shuttling of ER in the MCF7-TAMR cells but not the 1%MCF7.

Fig 6

1%MCF7 and MCF7-TAMR cells were treated for 24-hours with 1%FBS, dasatinib (100nM), 4-OHT (10nM), or the combination and stained with ER, pSrctyr416 and DAPI; bars indicate 20μm (A). Schematic diagram showing cross-talk between non-genomic ER and Src. ER associates with Src at the cell membrane via a non-genomic mechanism. This leads to an increase in both ERK1/2 and AKT providing a survival advantage. The reduced genomic activity of ER in this setting enhances resistance to tamoxifen. Inhibition of Src with dasatinib causes ER to shuttle to the nucleus where it is targeted by tamoxifen, leading to a decrease in proliferation and re-sensitization to the endocrine agent (B).