Harnessing the power of Calculus bovis: Anti-cancer properties and Wnt pathway modulation in hepatocellular carcinoma

Figure 1 The Wnt signaling pathway. A: Role of M2 macrophages in tumor progression: (1) Tumor cells induce the release of chemokines or cytokines; (2) Extravasation of monocytes from the blood vessels; (3) Macrophages are polarized to M1 type (pro-inflammatory); and (4) M2 type (anti-inflammatory) which causes induction of angiogenesis, anaerobic glycolysis, metastasis, invasion/migration, tumor proliferation and immune suppression; B: Representation of the Wnt signaling pathway in the activated and inactivated state and the role of Wnt signaling in different cancer hallmarks for tumor progression. Immune suppression: Tumor-associated macrophage (TAM) intrinsic β catenin signaling; Invasion/migration: TAM intrinsic β catenin signaling (Wnt 5a, Wnt 5b, Wnt 7b); Metastasis: Wnt 1, Wnt 2b, Wnt 3a; Tumor proliferation: TAM intrinsic β catenin signaling (Wnt 1, Wnt 3a, Wnt 5a, Wnt 5b); IFN: Interferon; TNF-α: Tumour necrosis factor-α; GM-CSF: Granulocyte macrophage colony stimulating factor; M-CSF: Macrophage colony-stimulating factor; LPS: Lipopolysaccharide; LRP: Lipoprotein receptor-related protein; GSK-3β: Glycogen synthase kinase-3β; CKIα: Casein kinase Iα; APC: Adenomatous polyposis coli; TCF: T cell factor; LEF: Lymphoid enhancer factor.