Skip to main content
. 2022 Mar 17;12:850732. doi: 10.3389/fonc.2022.850732

Figure 2.

Figure 2

Signaling pathways involved in drug resistance in cholangiocarcinoma. (A) Wnt/β-catenin signal pathway in drug resistance in cholangiocarcinoma: Wnt binds to its receptor-Frizzled to activate Dsh protein, which phosphorylate and inactivate GSK3β, facilitating the translocation of free and unphosphorylated β-catenin from the cytoplasm to the nucleus, where β-catenin binds to TCF/LEF to promote MDR1 expression. (B) Notch signal pathway in drug resistance in cholangiocarcinoma: After Notch activation, γ-secretase (Presenilin and Nicastrin) cleaves Notch COOH-terminal fragment. NICD, released into the cytoplasm, further translocate to the nucleus, where NICD interact with SKIP and CSL, leading to SMRT/HDACs dissociation and converting CSL to a transcriptional activator to initiate the expression of ABCC1, MRP1 and Sox9, which can further promote the expression of ABCB1 and ABCC4. (C) NF-kB signaling pathway in drug resistance in cholangiocarcinoma: NF-kB translocate into the nuclear to initiate the expression of ABCB1, ABCC1 and ABCG2.