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Review
. 2020 Dec 4;13(1):165.
doi: 10.1186/s13045-020-00990-3.

Targeting the Wnt/β-catenin signaling pathway in cancer

Ya Zhang  1   2   3   4   5   6 , Xin Wang  7   8   9   10   11   12
Affiliations
Review

Targeting the Wnt/β-catenin signaling pathway in cancer

Ya Zhang et al. J Hematol Oncol. .

Abstract

The aberrant Wnt/β-catenin signaling pathway facilitates cancer stem cell renewal, cell proliferation and differentiation, thus exerting crucial roles in tumorigenesis and therapy response. Accumulated investigations highlight the therapeutic potential of agents targeting Wnt/β-catenin signaling in cancer. Wnt ligand/ receptor interface, β-catenin destruction complex and TCF/β-catenin transcription complex are key components of the cascade and have been targeted with interventions in preclinical and clinical evaluations. This scoping review aims at outlining the latest progress on the current approaches and perspectives of Wnt/β-catenin signaling pathway targeted therapy in various cancer types. Better understanding of the updates on the inhibitors, antagonists and activators of Wnt/β-catenin pathway rationalizes innovative strategies for personalized cancer treatment. Further investigations are warranted to confirm precise and secure targeted agents and achieve optimal use with clinical benefits in malignant diseases.

Keywords: Cancer; Cancer stem cell; Targeted therapy; Wnt/β-catenin signaling pathway.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Schematic representation of activated and inhibited Wnt/β-catenin pathway. “WNT ON state”: Upon ligation of Wnts to their receptors composed of frizzled proteins and LRP5/6, the cytoplasmic protein DVL is activated and induces the suppression of GSK3β. Subsequently, stabilized β-catenin translocates into the nucleus and binds to TCF/LEF transcription factors to lead to target gene transcription. “WNT OFF state”: In the absence of WNT ligand, the destruction complex of β-catenin, a tertiary complex formed by AXIN, CK1α, GSK3β and APC, phosphorylates β-catenin, which subsequently undergoes the ubiquitin-proteasomal degradation
Fig. 2
Fig. 2
Hallmarks of diverse categories of Wnt/β-catenin targeted agents in cancer
Fig. 3
Fig. 3
Graphic overview of Wnt/β-catenin signaling pathway targeted interventions in cancer studies. Promising therapeutics targeting Wnt ligand/ receptor interface, β-catenin destruction complex and TCF/β-catenin transcription complex are investigated in preclinical and clinical evaluations
Fig. 4
Fig. 4
The schematic model of abnormal activation of the Wnt/β-catenin pathway promoting cancer stem cell progression and thus leading to the deterioration and metastasis of cancer
See this image and copyright information in PMC

References

    1. Salik B, Yi H, Hassan N, Santiappillai N, Vick B, Connerty P, Duly A, Trahair T, Woo A, Beck D et al: Targeting RSPO3-LGR4 signaling for leukemia stem cell eradication in acute myeloid leukemia. Cancer Cell 2020. - PubMed
    1. Soleas J, D'Arcangelo E, Huang L, Karoubi G, Nostro M, McGuigan A, Waddell T. Assembly of lung progenitors into developmentally-inspired geometry drives differentiation via cellular tension. Biomaterials. 2020;254:120128. doi: 10.1016/j.biomaterials.2020.120128. - DOI - PubMed
    1. Choi B, Cave C, Na C, Sockanathan S. GDE2-dependent activation of canonical wnt signaling in neurons regulates oligodendrocyte maturation. Cell Rep. 2020;31(5):107540. doi: 10.1016/j.celrep.2020.107540. - DOI - PMC - PubMed
    1. Zhang M, Weng W, Zhang Q, Wu Y, Ni S, Tan C, Xu M, Sun H, Liu C, Wei P, et al. The lncRNA NEAT1 activates Wnt/β-catenin signaling and promotes colorectal cancer progression via interacting with DDX5. J Hematol Oncol. 2018;11(1):113. doi: 10.1186/s13045-018-0656-7. - DOI - PMC - PubMed
    1. Cao M-Q, You AB, Zhu X-D, Zhang W, Zhang Y-Y, Zhang S-Z, Zhang K-W, Cai H, Shi W-K, Li X-L, et al. miR-182-5p promotes hepatocellular carcinoma progression by repressing FOXO3a. J Hematol Oncol. 2018;11(1):12. doi: 10.1186/s13045-018-0555-y. - DOI - PMC - PubMed

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