CCL2 and breast cancer: In addition, studies on the relationship between E2 and breast cancer showed that E2 can upregulate the transcription factor TWIST1 (a member of the basic helix-loop-helix transcription factor family) and NF-κB by activating the ERα/PI3K (phosphatidylinositol 3-hydroxy kinase)/AKT/NF-κB signal transduction pathway, thus positively regulating C-C motif chemokine ligand 2 (CCL2) synthesis and autocrine signaling to promote the proliferation, migration and invasion of ER+ breast cancer cells [49] (Fig. 2).