The newly identified GLI1/DNMTs axis set a bridge between Hh signaling pathway and epigenetics, which would help to elucidate the underling molecular mechanism in the development of PC, and may provide new therapeutic targets or biomarkers for earlier diagnosis. PE, together with PPE, are peculiar mycobacterial proteins over-represented in pathogenic mycobacterial species. Despite lacking typical secretion signals, both PE and PPE are secreted or located in the mycobacterial envelope. PE proteins can be divided into three distinct subfamilies, of which the most abundant is represented by PE_PGRS. All PE proteins are characterized by an N-terminal highly conserved domain of about 110 amino acids, named PE after the conserved signature motif Pro-Glu present near the N-terminus. In PE_PGRS proteins, the PE domain is followed by a C-terminal domain with a highly variable Gly-Ala rich sequence, which has been suggested to be involved in antigenic variation. In the other PE proteins the PE domain can be followed by an unrelated Cterminal domain, or the PE domain represents the entire protein. In the latter case the PE-encoding gene is usually in tandem with a PPE-encoding gene, and at least in one case the PE and PPE domains encoded by the coupled genes have been shown to interact. Hardly any of the about 100 PE proteins encoded by the Mycobacterium tuberculosis genome have been associated with a physiological function, with the exceptions of LipY, whose C-terminal domain shows lipase activity, PE_PGRS11, which was recently shown to encode a functional phosphoglycerate mutase and PE_PGRS33, which might be involved in induction of macrophage necrosis and apoptosis through interaction with Toll-like receptor 2. We recently showed that PE_PGRS33 is surface exposed when expressed in Mycobacterium smegmatis and that its PE domain contains the information necessary for the surface exposure. Chimeric proteins based on this PE domain were expressed on the M. smegmatis and Mycobacterium bovis BCG cell surface, and this feature was used to develop a surface delivery system to express heterologous antigen on M. bovis BCG envelope and increase its immunogenic potential. As already mentioned, although most PE and PPE proteins lack classical secretion signals, many are exported to the mycobacterial surface, suggesting the involvement of a novel secretory pathway. PLX-4720 Interestingly, in Mycobacterium marinum their secretion has recently been linked to ESX-5, a member of a novel family of secretion systems typical of mycobacteria. PE are exported mycobacterial proteins characterized by a well conserved N-terminal domain of about 100 amino acids that we recently showed to be required for their export. The lack in the PE domains of clear secretion signals led to the hypothesis that these proteins might be secreted through a new type of mycobacterial-specific secretion system. Indeed, it was recently showed that in M. marinum PE protein secretion is abrogated in mutants lacking the type VII secretion system ESX-5.