For example, annexin A2 (gene ANXA2) plays a key role in EMT and metastasis to the bone87; keratin 8 (KRT8) is a keratin expressed in hybrid EMT states7; the small heat shock protein Hsp27 (HSPB1) is a regulator of EMT and determining factor in breast cancer stem cells with functions during bone metastasis88,89; tissue inhibitor of metalloproteinase-1 (TIMP1) can promote EMT, and higher expression of EpCAM and TIMP1 was reported for breast primary tumors, circulating tumor cells, and metastases90,91. This evidence concerns the gene TIMP1 and breast cancer.