Research Team for Geriatric Medicine (Vascular Medicine), Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan.
Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan.
Int J Mol Sci. 2021 May 11;22(10):5076. doi: 10.3390/ijms22105076.
At the plasma membrane, gangliosides, a group of glycosphingolipids, are expressed along with glycosphingolipids, phospholipids, and cholesterol in so-called lipid rafts that interact with signaling receptors and related molecules. Most cancers present abnormalities in the intracellular signal transduction system involved in tumor growth, invasion, and metastasis. To date, the roles of gangliosides as regulators of signal transduction have been reported in several cancer types. Gangliosides can be expressed by the exogenous ganglioside addition, with their endogenous expression regulated at the enzymatic level by targeting specific glycosyltransferases. Accordingly, the relationship between changes in the composition of cell surface gangliosides and signal transduction has been investigated by controlling ganglioside expression. In cancer cells, several types of signaling molecules are positively or negatively regulated by ganglioside expression levels, promoting malignant properties. Moreover, antibodies against gangliosides have been shown to possess cytotoxic effects on ganglioside-expressing cancer cells. In the present review, we highlight the involvement of gangliosides in the regulation of cancer cell signaling, and we explore possible therapies targeting ganglioside-expressing cancer.
在质膜上，神经节苷脂是一组糖脂，与糖脂、磷脂和胆固醇一起存在于所谓的脂筏中，与信号受体和相关分子相互作用。大多数癌症在涉及肿瘤生长、侵袭和转移的细胞内信号转导系统中存在异常。迄今为止，神经节苷脂作为信号转导调节剂的作用已在几种癌症类型中得到报道。神经节苷脂可以通过外源性神经节苷脂添加表达，其内源性表达可以通过靶向特定糖基转移酶在酶水平上进行调节。因此，通过控制神经节苷脂的表达，研究了细胞表面神经节苷脂组成的变化与信号转导之间的关系。在癌细胞中，几种类型的信号分子的表达水平受到神经节苷脂的正向或负向调节，促进了恶性特性。此外，针对神经节苷脂的抗体已被证明对表达神经节苷脂的癌细胞具有细胞毒性作用。在本综述中，我们强调了神经节苷脂在调节癌细胞信号转导中的作用，并探讨了针对表达神经节苷脂的癌症的可能治疗方法。
