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

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...

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Autores principales: Shang, Shuang, Hua, Fang, Hu, Zhuo-Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464927/
https://www.ncbi.nlm.nih.gov/pubmed/28430641
http://dx.doi.org/10.18632/oncotarget.15687
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author Shang, Shuang
Hua, Fang
Hu, Zhuo-Wei
author_facet Shang, Shuang
Hua, Fang
Hu, Zhuo-Wei
author_sort Shang, Shuang
collection PubMed
description 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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spelling pubmed-54649272017-06-21 The regulation of β-catenin activity and function in cancer: therapeutic opportunities Shang, Shuang Hua, Fang Hu, Zhuo-Wei Oncotarget Review 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. Impact Journals LLC 2017-02-25 /pmc/articles/PMC5464927/ /pubmed/28430641 http://dx.doi.org/10.18632/oncotarget.15687 Text en Copyright: © 2017 Shang et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Review
Shang, Shuang
Hua, Fang
Hu, Zhuo-Wei
The regulation of β-catenin activity and function in cancer: therapeutic opportunities
title The regulation of β-catenin activity and function in cancer: therapeutic opportunities
title_full The regulation of β-catenin activity and function in cancer: therapeutic opportunities
title_fullStr The regulation of β-catenin activity and function in cancer: therapeutic opportunities
title_full_unstemmed The regulation of β-catenin activity and function in cancer: therapeutic opportunities
title_short The regulation of β-catenin activity and function in cancer: therapeutic opportunities
title_sort regulation of β-catenin activity and function in cancer: therapeutic opportunities
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464927/
https://www.ncbi.nlm.nih.gov/pubmed/28430641
http://dx.doi.org/10.18632/oncotarget.15687
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