Dataset Information

Direct Targeting of ?-Catenin by a Small Molecule Stimulates Proteasomal Degradation and Suppresses Oncogenic Wnt/?-Catenin Signaling.

ABSTRACT: The Wnt/?-catenin signaling pathway plays a major role in tissue homeostasis, and its dysregulation can lead to various human diseases. Aberrant activation of ?-catenin is oncogenic and is a critical driver in the development and progression of human cancers. Despite the significant potential of targeting the oncogenic ?-catenin pathway for cancer therapy, the development of specific inhibitors remains insufficient. Using a T cell factor (TCF)-dependent luciferase-reporter system, we screened for small-molecule compounds that act against Wnt/?-catenin signaling and identified MSAB (methyl 3-{[(4-methylphenyl)sulfonyl]amino}benzoate) as a selective inhibitor of Wnt/?-catenin signaling. MSAB shows potent anti-tumor effects selectively on Wnt-dependent cancer cells in vitro and in mouse cancer models. MSAB binds to ?-catenin, promoting its degradation, and specifically downregulates Wnt/?-catenin target genes. Our findings might represent an effective therapeutic strategy for cancers addicted to the Wnt/?-catenin signaling pathway.

SUBMITTER: Hwang SY

PROVIDER: S-EPMC4957947 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Publications

Direct Targeting of β-Catenin by a Small Molecule Stimulates Proteasomal Degradation and Suppresses Oncogenic Wnt/β-Catenin Signaling.

Hwang So-Young SY Deng Xianming X Byun Sanguine S Lee Chan C Lee Seung-Joo SJ Suh Hyunsuk H Zhang Jianming J Kang Qiaofeng Q Zhang Ting T Westover Kenneth D KD Mandinova Anna A Lee Sam W SW

Cell reports 20160616 1

The Wnt/β-catenin signaling pathway plays a major role in tissue homeostasis, and its dysregulation can lead to various human diseases. Aberrant activation of β-catenin is oncogenic and is a critical driver in the development and progression of human cancers. Despite the significant potential of targeting the oncogenic β-catenin pathway for cancer therapy, the development of specific inhibitors remains insufficient. Using a T cell factor (TCF)-dependent luciferase-reporter system, we screened fo ...[more]

PMID: 27320923

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Dataset Information

Direct Targeting of ?-Catenin by a Small Molecule Stimulates Proteasomal Degradation and Suppresses Oncogenic Wnt/?-Catenin Signaling.

Publications

Direct Targeting of β-Catenin by a Small Molecule Stimulates Proteasomal Degradation and Suppresses Oncogenic Wnt/β-Catenin Signaling.

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