Recent work using cultured UOK257 cells, FLCN knock-out mice, and BHD patient tumours showed that FLCN inactivation also increases the activity of a nucleo-cytoplasmic transcription factor (TFE3) that has previously been implicated in renal cell carcinoma (Hong et al., 2010b). Additional work in the same laboratory used in vitro cell based assays, in vitro xenograft studies and gene expression profiles to demonstrate that FLCN has an essential role in the regulation of TGF-β signalling (Hong et al., 2010a). Experiments by Cash et al. (2011) took this connection further by demonstrating that FLCN appears to regulate apoptosis through TGF-β-dependent transcription, which could help to further explain the renal cancer phenotype observed in BHD syndrome.
While the finer details still need investigating, it is clear that Folliculin is involved in a dense signalling network, and that unravelling this network will help open up many new avenues for potential therapies to help alleviate and ultimately cure the symptoms caused by BHD syndrome.
