ESR1 and breast cancer: Work with HER2+ BC cell lines, SKBR-3 (ER-, PR-) and BT474 (ER+, PR+) has shown that CHD4 depletion leads to a significant inhibition of cell proliferation, inducing p27KIP1 up-regulation, Tyr1248 HER2 phosphorylation, ERK1/2 and AKT dephosphorylation, as well as the downregulation of both HER2 and PI3K (62) (Figure 2C).