Aberrant activation of Sonic hedgehog signaling in chronic cholecystitis and gallbladder carcinoma

Targeting specific molecular pathways holds promise for advanced gallbladder cancer therapy

“…Recent studies have confirmed that aberrant activation of Shh signaling transduction is present in GBC [56][57][58]. Overexpression of Shh, Smoothened (Smo), Patched (Ptch) and Gli1 has been found with great frequency in GBC (46-97%, 65%, 75-97% and 50-97%, respectively) ( Table 1).…”

“…Li et al [58] found an association between Shh, Patched (Ptch) and Gli1 expression and poor survival. A similar study reported that only Gli1 expression is associated with poor prognosis [56]. Xie et al presented an interesting perspective about the Shh pathway.…”

“…Overexpression 97% [56], 51.3% [57], 70% [58] Poor prognosis [56,58] [45]. 38.5% [109] Poor prognosis [109] Amplification 9% [45] HER2 (ERRB2) Mutation 9.8% [33] Early event [113] Overexpression 13.8% [110].…”

“…Xie et al presented an interesting perspective about the Shh pathway. They found that aberrant expression of Ptch and Gli1 in chronic cholecystitis (CC) correlated with inflammatory levels and suggested that this altered pathway may be involved in the course of development from CC to GBC [56]. Furthermore, preclinical evidence has shown that inhibition of Smo decreases the proliferation and invasiveness of GBC cells through the inhibition of MMP2 and MMP9 expression and epithelial-mesenchymal transition [57].…”

Adenocarcinoma of the Gallbladder: Risk Factors and Pathogenic Pathways

“…In CG, c-Met is immunohistochemically localized in the cell membrane (Sanada et al 2010). CG also showed an aberrant activation of the Sonic hedgehog signaling pathway (Xie et al 2014). ErbB2 signaling in CG is linked to MUC4 expression, as ErbB2 interacts with MUC4 at the carcinoma cell apex, associated with hyperphosphorylation of erbB2, MAPK, and Akt, and with the overexpression of cyclooxygenase-2.…”