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 G0 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, conta...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1160415/full |
| _version_ | 1827989128879276032 |
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| author | Sotai Kimura Tomoka Morita Kosuke Hosoba Kosuke Hosoba Hiroshi Itoh Takashi Yamamoto Takashi Yamamoto Tatsuo Miyamoto |
| author_facet | Sotai Kimura Tomoka Morita Kosuke Hosoba Kosuke Hosoba Hiroshi Itoh Takashi Yamamoto Takashi Yamamoto Tatsuo Miyamoto |
| author_sort | Sotai Kimura |
| collection | DOAJ |
| description | Primary cilium is a non-motile, antenna-like structure that develops in the quiescent G0 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. |
| first_indexed | 2024-04-10T00:14:28Z |
| format | Article |
| id | doaj.art-7283c68481f34dcb97164ce1b7f0dbe7 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-10T00:14:28Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-7283c68481f34dcb97164ce1b7f0dbe72023-03-16T06:00:42ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-03-011010.3389/fmolb.2023.11604151160415Cholesterol in the ciliary membrane as a therapeutic target against cancerSotai Kimura0Tomoka Morita1Kosuke Hosoba2Kosuke Hosoba3Hiroshi Itoh4Takashi Yamamoto5Takashi Yamamoto6Tatsuo Miyamoto7Department of Molecular Pathology, Graduate School of Medicine, Yamaguchi University, Ube, JapanDepartment of Molecular and Cellular Physiology, Graduate School of Medicine, Yamaguchi University, Ube, JapanProgram of Biomedical Science, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, JapanProgram of Mathematical and Life Science, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, JapanDepartment of Molecular Pathology, Graduate School of Medicine, Yamaguchi University, Ube, JapanProgram of Biomedical Science, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, JapanProgram of Mathematical and Life Science, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, JapanDepartment of Molecular and Cellular Physiology, Graduate School of Medicine, Yamaguchi University, Ube, JapanPrimary cilium is a non-motile, antenna-like structure that develops in the quiescent G0 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.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1160415/fullprimary ciliacholesterolcancerssonic hedgehog signalWnt signal |
| spellingShingle | Sotai Kimura Tomoka Morita Kosuke Hosoba Kosuke Hosoba Hiroshi Itoh Takashi Yamamoto Takashi Yamamoto Tatsuo Miyamoto Cholesterol in the ciliary membrane as a therapeutic target against cancer Frontiers in Molecular Biosciences primary cilia cholesterol cancers sonic hedgehog signal Wnt signal |
| 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 | primary cilia cholesterol cancers sonic hedgehog signal Wnt signal |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1160415/full |
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