2. Academic Validation
  3. Liquidambaric acid inhibits Wnt/β-catenin signaling and colon cancer via targeting TNF receptor-associated factor 2

Liquidambaric acid inhibits Wnt/β-catenin signaling and colon cancer via targeting TNF receptor-associated factor 2

  • Cell Rep. 2022 Feb 1;38(5):110319. doi: 10.1016/j.celrep.2022.110319.
Rong Yan 1,  Hongyan Zhu 1,  Piao Huang 1,  Min Yang 1,  Mengzhen Shen 1,  Yuting Pan 1,  Chengqian Zhang 2,  Xianglian Zhou 1,  Huiliang Li 3,  Xisong Ke 4,  Weidong Zhang 5,  Piliang Hao 6,  Yi Qu 7
Affiliations

Affiliations

  • 1 Center for Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, No.1200 Cailun Road, Shanghai 201203, P.R. China; Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, No.1200 Cailun Road, Shanghai 201203, China.
  • 2 School of Life Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai 201210, P.R. China.
  • 3 School of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Shanghai 200433, P.R. China.
  • 4 Center for Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, No.1200 Cailun Road, Shanghai 201203, P.R. China; Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, No.1200 Cailun Road, Shanghai 201203, China. Electronic address: xisongke@shutcm.edu.cn.
  • 5 Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, No.1200 Cailun Road, Shanghai 201203, China; School of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Shanghai 200433, P.R. China. Electronic address: wdzhangy@hotmail.com.
  • 6 School of Life Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai 201210, P.R. China. Electronic address: haopl@shanghaitech.edu.cn.
  • 7 Center for Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, No.1200 Cailun Road, Shanghai 201203, P.R. China; Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, No.1200 Cailun Road, Shanghai 201203, China. Electronic address: yiqu@shutcm.edu.cn.
PMID: 35108540 DOI: 10.1016/j.celrep.2022.110319
Abstract

Wnt/β-catenin signaling is a well-established driver of colon cancer; however, a targeted therapeutic agent has not reached clinics yet. In the present study, we report that the natural compound liquidambaric acid (LDA) inhibits oncogenic Wnt/β-catenin signaling in vitro and in vivo through its direct target tumor necrosis factor receptor-associated factor 2 (TRAF2). Mechanistically, TRAF2 positively regulates Wnt signaling by interacting with the N-terminal of β-catenin via its TRAF-C domain; this interaction is disrupted in presence of LDA. Particularly, a TRAF2/β-catenin/TCF4/TNIK complex is present in colon Cancer cells, where TRAF2 is indispensable for the complex formation, and TRAF2/β-catenin and β-catenin/TCF4 interactions are disrupted upon LDA treatment. Our findings not only highlight that TRAF2 is an oncogenic regulator of Wnt/β-catenin signaling and colon Cancer but also provide a lead compound targeting TRAF2 for Cancer therapy.

Keywords

TRAF2; TRAF2/β-catenin/TCF4/TNIK complex; Wnt/β-catenin signaling; colorectal cancer; liquidambaric acid.

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