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. 2020 Feb;52(2):183-191.
doi: 10.1038/s12276-020-0380-6. Epub 2020 Feb 10.

Wnt Signaling in Cancer: Therapeutic Targeting of Wnt Signaling Beyond β-Catenin and the Destruction Complex

Free PMC article

Wnt Signaling in Cancer: Therapeutic Targeting of Wnt Signaling Beyond β-Catenin and the Destruction Complex

Youn-Sang Jung et al. Exp Mol Med. .
Free PMC article


Wnt/β-catenin signaling is implicated in many physiological processes, including development, tissue homeostasis, and tissue regeneration. In human cancers, Wnt/β-catenin signaling is highly activated, which has led to the development of various Wnt signaling inhibitors for cancer therapies. Nonetheless, the blockade of Wnt signaling causes side effects such as impairment of tissue homeostasis and regeneration. Recently, several studies have identified cancer-specific Wnt signaling regulators. In this review, we discuss the Wnt inhibitors currently being used in clinical trials and suggest how additional cancer-specific regulators could be utilized to treat Wnt signaling-associated cancer.

Conflict of interest statement

The authors declare that they have no conflict of interest.


Fig. 1
Fig. 1
Wnt/β-catenin signaling inhibitors in current and past clinical trials (also see Table 1).
Fig. 2
Fig. 2. Inhibition of Wnt/β-catenin signaling activity by targeting the TMEM9-v-ATPase axis.
TMEM9 expression is highly increased in CRC. As an amplifier of Wnt/β-catenin signaling, TMEM9 facilitates the assembly of v-ATPase, resulting in vesicular acidification and subsequent lysosomal degradation of APC. Then, the increased β-catenin transactivates Wnt target genes. The inhibition of TMEM9-v-ATPase-induced vesicular acidification by bafilomycin and concanamycin efficiently inhibits APC lysosomal degradation, which leads to the suppression of Wnt/β-catenin gene activation in cancer cells.

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