EGFR is expressed in almost all nonneoplastic cell types in TME, including CAFs, except mature cells in the lymphohematopoietic system.245,246 GPER was first reported as a GPCR gene in breast cancer,247 and Luo et al. found that GPER expression was abundant in breast CAFs.248 G15 (a selective GPER antagonist), AG (an inhibitor of EGFR), and U0126 (an inhibitor of ERK1/2) significantly inhibited GPER-mediated proliferation and cell cycle changes in breast CAFs induced by E2, G1, and tamoxifen,248 implying that GPER/EGFR/ERK signaling pathway was activated in this process. The gene discussed is MAPK1; the disease is breast cancer.