Gene Expression and Proteome Analysis as Sources of Biomarkers in Basal Cell Carcinoma

Figure 1

Sonic hedgehog (SHH) signaling pathway. (a) In the absence of the HH ligand, PTCH1 represses signaling through SMO causing GLI to remain inactive in the cytoplasm. (b) During physiological activation of the pathway the HH ligand binds to PTCH1, ending SMO suppression and causing activation and nucleus translocation of GLI thus influencing target genes expression. (c) Pathological activation of the SHH pathway through loss or mutational inactivation of PTCH1, suspending SMO inhibition in Gorlin-Goltz and sporadic BCCs (twist, FOXM1, Wnt pathway molecules, and others are viable biomarkers in BCC proteomic studies). (d) SMO activating mutations, found in sporadic BCCs, showing similar effects on the SHH pathway. HH: sonic hedgehog ligand; PTCH: protein patched hedgehog receptor, SMO: smoothened receptor, GLI: GLI factor, and Wnt: wingless signaling pathway.

(a) Inactive

(b) Physiologically activated, ligand dependent, reversible

(c) Oncogenic signaling in BCC, ligand independent, PTCH1 loss or mutation

(d) Hedgehog pathway activation through SMO activating mutations