In addition to a potential loss of inhibitory sequestration of GEFH1 at TJ, increased expression of human pituitary tumour-transforming gene 1 (hPTTG1), a transcription factor overexpressed in many types of tumour, transcriptionally activates GEFH1 expression in a highly metastatic breast cancer cell-line (Liao et al., 2012) which may overcome the inhibitory capacity of TJ-bound cingulin (Fig. 2a). Here, ARHGEF2 is linked to neoplasm.