American Association for Cancer Research
Browse
mct-21-0801_supplementary_data_s1_supps1.pdf (527.51 kB)

Supplementary Data S1 from Inhibition of Wnt Signaling in Colon Cancer Cells via an Oral Drug that Facilitates TNIK Degradation

Download (527.51 kB)
journal contribution
posted on 2023-04-03, 19:02 authored by Kun Zhou, Jae Eun Cheong, Subrahmanian Tarakkad Krishnaji, Aram Ghalali, Haojie Fu, Lufei Sui, Catherine Alix-Panabières, Laure Cayrefourcq, Diane Bielenberg, Lijun Sun, Bruce Zetter

Supplementary figures and table

Funding

David H Koch Foundation

Boston Children's Hospital Technology and Innovation Development Office

History

ARTICLE ABSTRACT

We have synthesized an oxetane derivative of the benzimidazole compound mebendazole (OBD9) with enhanced solubility and strong anticancer activity in multiple types of cancer cells, especially colorectal cancer. In this report, we provide evidence that OBD9 suppresses colorectal cancer growth by interfering with the Wnt signaling pathway, a main driver of cell growth in colorectal cancer. Specifically, we find that OBD9 induces autophagic degradation of TNIK (traf2 and Nck-interacting kinase), which promotes T-cell factor-4 (TCF4)/beta-catenin–mediated gene expression. Thus, OBD9 as a TNIK inhibitor blocks Wnt/beta-catenin signaling at the final step of transcriptional activation. We suggest that OBD9 provides a potential novel autophagy-mediated, Wnt-damping therapeutic strategy for the treatment of colorectal cancer.

Usage metrics

    Molecular Cancer Therapeutics

    Categories

    Keywords

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC