Oncotarget

Reviews:

The regulation of β-catenin activity and function in cancer: therapeutic opportunities

Shuang Shang, Fang Hua and Zhuo-Wei Hu _

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Oncotarget. 2017; 8:33972-33989. https://doi.org/10.18632/oncotarget.15687

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Abstract

Shuang Shang1,*, Fang Hua1,* and Zhuo-Wei Hu1

1 Immunology and Cancer Pharmacology Group, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica; Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China

* These authors have contributed equally to this work

Correspondence to:

Zhuo-Wei Hu, email:

Keywords: Wnt signaling, protein stability, subcellular localization, transcriptional regulation, cancer therapy

Received: December 20, 2016 Accepted: February 15, 2017 Published: February 25, 2017

Abstract

Wnt/β-catenin signaling is an evolutionarily conserved and versatile pathway that is known to be involved in embryonic development, tissue homeostasis and a wide variety of human diseases. Aberrant activation of this pathway gives rise to the accumulation of β-catenin in the nucleus and promotes the transcription of many oncogenes such as c-Myc and CyclinD-1. As a result, it contributes to carcinogenesis and tumor progression of several cancers, including colon cancer, hepatocellular carcinoma, pancreatic cancer, lung cancer and ovarian cancer. β-Catenin is a pivotal component of the Wnt signaling pathway and it is tightly regulated at three hierarchical levels: protein stability, subcellular localization and transcriptional activity. Uncovering the regulatory mechanisms of β-catenin will provide new insights into the pathogenesis of cancer and other diseases, as well as new therapeutic strategies against these diseases. In this review we dissect the concrete regulatory mechanisms of β-catenin from three aspects mentioned above. Then we focus on the role of β-catenin in cancer initiation, progression, dormancy, immunity and cancer stem cell maintenance. At last, we summarize the recent progress in the development of agents for the pharmacological modulation of β-catenin activity in cancer therapy.


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