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Fig. 1 | Cancer Cell International

Fig. 1

From: Triple-negative breast cancer: understanding Wnt signaling in drug resistance

Fig. 1

An overview of the Wnt signaling pathway. a In the absence of Wnt ligands (Wnt-Off state), β-catenin is released from the cytomembrane, sequestered in a destructive protein complex, that is composed of adenomatous polyposis coli (APC), the scaffolding protein axin, casein kinase 1 (CK1), and glycogen synthase kinase 3β (GSK-3β). The Dkks, WIF, and SFRPs act as antagonists. The phosphorylations by CK1 and GSK-3β recruit β-propeller domain of the E3 ubiquitin ligase (β TrCP) and subsequently cause the β catenin proteasomal degradation and transcriptional repression of Wnt target genes. b Canonical Wnt/β-catenin signaling is activated by binding of Wnt ligands (Wnt-On state) to a receptor complex composed of FZD and LRP 5/6. The recruitment of phosphorylated DVL to FZD inhibits the APC/CK1/GSK-3β destruction complex and blockade of β-catenin by GSK-3β. Accumulated β-catenin in the cytoplasm translocate into the nucleus, where it regulates target gene expression with the Tcf/Lef family of transcription factors. c In Wnt planar cell polarity (Wnt-PCP) signaling, Wnt binds multiple receptors including FZD and co-receptors ROR and Ryk. This activates Rho-A and RAK1/Cdc42, which activate ROCK and JNK (c-Jun N-terminal kinase), respectively, leading to actin cytoskeleton rearrangement and cell polarity through AP-1. d In ON-state non-canonical Wnt/Ca2+ signaling pathway, the binding of Wnt promotes FZD-mediated activation of G proteins and Ryk and initiates the release of Ca2+ from intracellular stores and activation of Ca2+-dependent effector molecules. Several Ca2+-sensitive targets, i.e., PKC, CamKII, and calcineurin, have been identified as downstream of the Wnt/Ca2+ pathway

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