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. Author manuscript; available in PMC: 2021 Jan 21.
Published in final edited form as: Oncogene. 2020 Oct 30;40(2):322–333. doi: 10.1038/s41388-020-01530-6

Figure 7.

Figure 7.

EMT facilitates diverse RTK signaling through the upregulation of FGFR1 and NRP1. Transformation and breast cancer progression are driven by ErbB signaling through EGFR and HER2. These signaling pathways can be effectively blocked through the use of several small molecules that directly act on these RTKs, collectively referred to here as ErbB inhibition (ErbBi). Induction of epithelial-mesenchymal transition (EMT) is a shared mechanism of the acquired resistance to ErbBi. Through this process tumor cells originally driven by ErbB signaling upregulate FGFR1 and NRP1. FGFR1 can be directly targeted through the use of small molecule kinase inhibitors (FGFRi). In addition to FGFR1, NRP1 can also enhance signaling from other RTKs that are present such as PDGFR and the MET receptor. Twist-mediated expression of NRP1 during EMT requires BRD4 binding to acetylated H3K27. Therefore, use of BET inhibitors such as JQ1 in conjunction with targeted inhibition of FGFR may present an effective means to block ErbBi bypass signaling.