Activation of matrix metalloproteinase-26 by HOXA10 promotes embryo adhesion in vitro

• Matrix metalloproteinase-26 (MMP-26) is a novel downstream target gene of HOXA10 in human endometrial cells.
• HOXA10 binds directly to a conserved TTAT unit (−442 to −439) of the MMP-26 gene promoter.
• HOXA10 is required for hormone-induced MMP-26 expression and secretion.
• HOXA10-mediated expression of MMP-26 promotes embryo adhesion.

Successful embryonic implantation requires an effective maternal–embryonic molecular dialogue. However, the detailed mechanisms of epithelial-embryo adhesion remain poorly understood. Here, we report that matrix metalloproteinase-26 (MMP-26) is a novel downstream target gene of homeobox a 10 (HOXA10) in human endometrial cells. HOXA10 binds directly to a conserved TTAT unit (−442 to −439) located within the 5′ regulatory region of the MMP-26 gene and regulates the expression and secretion of MMP-26 in a concentration-dependent manner. Moreover, the adenovirus-mediated overexpression of MMP-26 in Ishikawa cells markedly increased BeWo spheroid adhesion. An antibody blocking assay further demonstrated that the promotion of BeWo spheroid adhesion by HOXA10 and MMP-26 was significantly inhibited by pre-treatment with a specific antibody against MMP-26. These results demonstrate that the HOXA10-mediated expression of MMP-26 promotes embryo adhesion during the process of embryonic implantation.