Fig. 8: CDH17-mediated regulation of LGR5 expression, Wnt signaling and drug resistance.
The interaction of CDH17 with α2β1 integrin regulates the expression of LGR5, which in turn enhances the Wnt/β-catenin signaling. This pathway drives cell proliferation and upregulates stem cell markers, as well as proteins involved in drug resistance, such as SLC38A5, through MYC activation. Any disruption of CDH17 expression or its interaction with integrins would destabilize this regulatory cascade. Moreover, amiloride, an inhibitor of SLC38A5, increases tumor cell susceptibility to chemotherapy agents and, likely, intracellular Ca2+ alterations that impact metastatic progression.
