Moreover, expression of TLX is rapidly downregulated by contact with blood vessels and a derangement of fibronectin matrix was observed in TLX-null mice.35 In this context, it is interesting to note that fibronectin fragments from cancer cells can induce the secretion of MMP-2,36 whereas MMP-2 and MMP-9 have been shown to degrade fibronectin, as the first step of ovarian cancer metastases.37 Thus, TLX affects not only immediate hypoxia-responsive proteins, that is, HIF-2α and VEGF, but also affects extracellular matrix proteins needed for vascular organization. This evidence concerns the gene NR2E1 and ovarian cancer.