Cholesterol in the ciliary membrane as a therapeutic target against cancer
Primary cilium is a non-motile, antenna-like structure that develops in the quiescent G(0) phase-cell surface. It is composed of an array of axonemal microtubules polymerized from the centrosome/basal body. The plasma membrane surrounding the primary cilium, which is called the ciliary membrane, con...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060879/ https://www.ncbi.nlm.nih.gov/pubmed/37006607 http://dx.doi.org/10.3389/fmolb.2023.1160415 |
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author | Kimura, Sotai Morita, Tomoka Hosoba, Kosuke Itoh, Hiroshi Yamamoto, Takashi Miyamoto, Tatsuo |
author_facet | Kimura, Sotai Morita, Tomoka Hosoba, Kosuke Itoh, Hiroshi Yamamoto, Takashi Miyamoto, Tatsuo |
author_sort | Kimura, Sotai |
collection | PubMed |
description | Primary cilium is a non-motile, antenna-like structure that develops in the quiescent G(0) phase-cell surface. It is composed of an array of axonemal microtubules polymerized from the centrosome/basal body. The plasma membrane surrounding the primary cilium, which is called the ciliary membrane, contains a variety of receptors and ion channels, through which the cell receives extracellular chemical and physical stimuli to initiate signal transduction. In general, primary cilia disappear when cells receive the proliferative signals to re-enter the cell cycle. Primary cilia thus cannot be identified in many malignant and proliferative tumors. In contrast, some cancers, including basal cell carcinoma, medulloblastoma, gastrointestinal stromal tumor, and other malignancies, retain their primary cilia. Importantly, it has been reported that the primary cilia-mediated oncogenic signals of Hedgehog, Wnt, and Aurora kinase A are involved in the tumorigenesis and tumor progression of basal cell carcinoma and some types of medulloblastoma. It has also been demonstrated that cholesterol is significantly more enriched in the ciliary membrane than in the rest of the plasma membrane to ensure Sonic hedgehog signaling. A series of epidemiological studies on statin drugs (cholesterol-lowering medication) demonstrated that they prevent recurrence in a wide range of cancers. Taken together, ciliary cholesterol could be a potential therapeutic target in primary cilia-dependent progressive cancers. |
format | Online Article Text |
id | pubmed-10060879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100608792023-03-31 Cholesterol in the ciliary membrane as a therapeutic target against cancer Kimura, Sotai Morita, Tomoka Hosoba, Kosuke Itoh, Hiroshi Yamamoto, Takashi Miyamoto, Tatsuo Front Mol Biosci Molecular Biosciences Primary cilium is a non-motile, antenna-like structure that develops in the quiescent G(0) phase-cell surface. It is composed of an array of axonemal microtubules polymerized from the centrosome/basal body. The plasma membrane surrounding the primary cilium, which is called the ciliary membrane, contains a variety of receptors and ion channels, through which the cell receives extracellular chemical and physical stimuli to initiate signal transduction. In general, primary cilia disappear when cells receive the proliferative signals to re-enter the cell cycle. Primary cilia thus cannot be identified in many malignant and proliferative tumors. In contrast, some cancers, including basal cell carcinoma, medulloblastoma, gastrointestinal stromal tumor, and other malignancies, retain their primary cilia. Importantly, it has been reported that the primary cilia-mediated oncogenic signals of Hedgehog, Wnt, and Aurora kinase A are involved in the tumorigenesis and tumor progression of basal cell carcinoma and some types of medulloblastoma. It has also been demonstrated that cholesterol is significantly more enriched in the ciliary membrane than in the rest of the plasma membrane to ensure Sonic hedgehog signaling. A series of epidemiological studies on statin drugs (cholesterol-lowering medication) demonstrated that they prevent recurrence in a wide range of cancers. Taken together, ciliary cholesterol could be a potential therapeutic target in primary cilia-dependent progressive cancers. Frontiers Media S.A. 2023-03-16 /pmc/articles/PMC10060879/ /pubmed/37006607 http://dx.doi.org/10.3389/fmolb.2023.1160415 Text en Copyright © 2023 Kimura, Morita, Hosoba, Itoh, Yamamoto and Miyamoto. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Kimura, Sotai Morita, Tomoka Hosoba, Kosuke Itoh, Hiroshi Yamamoto, Takashi Miyamoto, Tatsuo Cholesterol in the ciliary membrane as a therapeutic target against cancer |
title | Cholesterol in the ciliary membrane as a therapeutic target against cancer |
title_full | Cholesterol in the ciliary membrane as a therapeutic target against cancer |
title_fullStr | Cholesterol in the ciliary membrane as a therapeutic target against cancer |
title_full_unstemmed | Cholesterol in the ciliary membrane as a therapeutic target against cancer |
title_short | Cholesterol in the ciliary membrane as a therapeutic target against cancer |
title_sort | cholesterol in the ciliary membrane as a therapeutic target against cancer |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060879/ https://www.ncbi.nlm.nih.gov/pubmed/37006607 http://dx.doi.org/10.3389/fmolb.2023.1160415 |
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