Targeted inhibition of Wnt signaling with a Clostridioides difficile toxin B fragment suppresses breast cancer tumor growth
dc.contributor.author | He, Aina | |
dc.contributor.author | Tian, Songhai | |
dc.contributor.author | Kopper, Oded | |
dc.contributor.author | Horan, Daniel J. | |
dc.contributor.author | Chen, Peng | |
dc.contributor.author | Bronson, Roderick T. | |
dc.contributor.author | Sheng, Ren | |
dc.contributor.author | Wu, Hao | |
dc.contributor.author | Sui, Lufei | |
dc.contributor.author | Zhou, Kun | |
dc.contributor.author | Tao, Liang | |
dc.contributor.author | Wu, Quan | |
dc.contributor.author | Huang, Yujing | |
dc.contributor.author | Shen, Zan | |
dc.contributor.author | Han, Sen | |
dc.contributor.author | Chen, Xueqing | |
dc.contributor.author | Chen, Hong | |
dc.contributor.author | He, Xi | |
dc.contributor.author | Robling, Alexander G. | |
dc.contributor.author | Jin, Rongsheng | |
dc.contributor.author | Clevers, Hans | |
dc.contributor.author | Xiang, Dongxi | |
dc.contributor.author | Li, Zhe | |
dc.contributor.author | Dong, Min | |
dc.contributor.department | Anatomy, Cell Biology and Physiology, School of Medicine | |
dc.date.accessioned | 2024-04-16T14:33:31Z | |
dc.date.available | 2024-04-16T14:33:31Z | |
dc.date.issued | 2023-11-09 | |
dc.description.abstract | Wnt signaling pathways are transmitted via 10 homologous frizzled receptors (FZD1-10) in humans. Reagents broadly inhibiting Wnt signaling pathways reduce growth and metastasis of many tumors, but their therapeutic development has been hampered by the side effect. Inhibitors targeting specific Wnt-FZD pair(s) enriched in cancer cells may reduce side effect, but the therapeutic effect of narrow-spectrum Wnt-FZD inhibitors remains to be established in vivo. Here, we developed a fragment of C. difficile toxin B (TcdBFBD), which recognizes and inhibits a subclass of FZDs, FZD1/2/7, and examined whether targeting this FZD subgroup may offer therapeutic benefits for treating breast cancer models in mice. Utilizing 2 basal-like and 1 luminal-like breast cancer models, we found that TcdBFBD reduces tumor-initiating cells and attenuates growth of basal-like mammary tumor organoids and xenografted tumors, without damaging Wnt-sensitive tissues such as bones in vivo. Furthermore, FZD1/2/7-positive cells are enriched in chemotherapy-resistant cells in both basal-like and luminal mammary tumors treated with cisplatin, and TcdBFBD synergizes strongly with cisplatin in inhibiting both tumor types. These data demonstrate the therapeutic value of narrow-spectrum Wnt signaling inhibitor in treating breast cancers. | |
dc.eprint.version | Final published version | |
dc.identifier.citation | He A, Tian S, Kopper O, et al. Targeted inhibition of Wnt signaling with a Clostridioides difficile toxin B fragment suppresses breast cancer tumor growth. He A, Tian S, Kopper O, et al. Targeted inhibition of Wnt signaling with a Clostridioides difficile toxin B fragment suppresses breast cancer tumor growth. PLoS Biol. 2023;21(11):e3002353. Published 2023 Nov 9. doi:10.1371/journal.pbio.3002353. 2023;21(11):e3002353. Published 2023 Nov 9. doi:10.1371/journal.pbio.3002353 | |
dc.identifier.uri | https://hdl.handle.net/1805/40048 | |
dc.language.iso | en_US | |
dc.publisher | Public Library of Science | |
dc.relation.isversionof | 10.1371/journal.pbio.3002353 | |
dc.relation.journal | PLoS Biology | |
dc.rights | Attribution 4.0 International | en |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | PMC | |
dc.subject | Bacterial toxins | |
dc.subject | Breast neoplasms | |
dc.subject | Clostridioides difficile | |
dc.subject | Cisplatin | |
dc.subject | Wnt signaling pathway | |
dc.title | Targeted inhibition of Wnt signaling with a Clostridioides difficile toxin B fragment suppresses breast cancer tumor growth | |
dc.type | Article |