ESR1 and breast cancer: Given that the AnxA6 promoter is heavily methylated, for example in EGFR-overexpressing A431 and ER-negative MDA-MB-468 breast cancer cells, both of which with relatively low AnxA6 levels [19], these effects may be mediated via epigenetic mechanisms including inhibition of DNA methyltransferases and/or histone deacetylases.