Kimura Sotai, Morita Tomoka, Hosoba Kosuke, Itoh Hiroshi, Yamamoto Takashi, Miyamoto Tatsuo
Department of Molecular Pathology, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
Department of Molecular and Cellular Physiology, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
Front Mol Biosci. 2023 Mar 16;10:1160415. doi: 10.3389/fmolb.2023.1160415. eCollection 2023.
Primary cilium is a non-motile, antenna-like structure that develops in the quiescent G 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.
初级纤毛是一种非运动性的、天线样结构，在静止的G期细胞表面形成。它由从中心体/基体聚合而来的一束轴丝微管组成。围绕初级纤毛的质膜称为纤毛膜，含有多种受体和离子通道，细胞通过这些受体和离子通道接收细胞外化学和物理刺激以启动信号转导。一般来说，当细胞接收到增殖信号重新进入细胞周期时，初级纤毛会消失。因此，在许多恶性和增殖性肿瘤中无法识别初级纤毛。相反，一些癌症，包括基底细胞癌、髓母细胞瘤、胃肠道间质瘤和其他恶性肿瘤，保留了它们的初级纤毛。重要的是，据报道，初级纤毛介导的刺猬信号通路、Wnt信号通路和极光激酶A的致癌信号参与了基底细胞癌和某些类型髓母细胞瘤的肿瘤发生和肿瘤进展。还证明，纤毛膜中的胆固醇比质膜的其他部分显著富集，以确保音猬因子信号传导。一系列关于他汀类药物（降胆固醇药物）的流行病学研究表明，它们可以预防多种癌症的复发。综上所述，纤毛胆固醇可能是原发性纤毛依赖性进展性癌症的潜在治疗靶点。
