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. Author manuscript; available in PMC: 2023 Jul 24.
Published in final edited form as: Trends Pharmacol Sci. 2023 Feb 23;44(4):222–236. doi: 10.1016/j.tips.2023.01.003

Figure II. Metastasis-initiating cells (MICs) in colorectal cancer.

Figure II.

Metastases arise from a subset of tumor cells that have acquired invasiveness due to the activation of the NOTCH, Wnt/β-catenin, and TGF-β signaling pathways. Interaction between JAGGED (expressed by endothelial cells) and NOTCH (expressed by the tumor cells) allow for survival of the tumor cells around tumor vessels. Loss of APC or Axin promotes Wnt/β-catenin signaling and induce dedifferentiation and stemness of the MICs. MICs are resistant to the cytostatic effects of TGF-β signaling, which can also create an immune-suppressive microenvironment and further promote invasion of MICs. Abbreviations: TGF-β, transforming growth factor-β; β-cat, β-catenin; NICD, Notch intracellular domain; APC, adenomatous polyposis coli; T-reg, regulatory T-cell; MDSC, myeloid-derived suppressor cell; CAF, cancer-associated fibroblast.