Department of Tumor Biology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.
Cancer Biology Ph.D. Program, University of South Florida, Tampa, Florida, USA.
Mol Carcinog. 2022 May;61(5):439-453. doi: 10.1002/mc.23394. Epub 2022 Feb 2.
l-fucose is a dietary sugar that is used by cells in a process called fucosylation to posttranslationally modify and regulate protein behavior and function. As fucosylation plays essential cellular functions in normal organ and immune developmental and homeostasis, it is perhaps not surprising that it has been found to be perturbed in a number of pathophysiological contexts, including cancer. Increasing studies over the years have highlighted key roles that altered fucosylation can play in cancer cell-intrinsic as well as paracrine signaling and interactions. In particular, studies have demonstrated that fucosylation impact tumor:immunological interactions and significantly enhance or attenuate antitumor immunity. Importantly, fucosylation appears to be a posttranslational modification that can be therapeutically targeted, as manipulating the molecular underpinnings of fucosylation has been shown to be sufficient to impair or block tumor progression and to modulate antitumor immunity. Moreover, the fucosylation of anticancer agents, such as therapeutic antibodies, has been shown to critically impact their efficacy. In this review, we summarize the underappreciated roles that fucosylation plays in cancer and immune cells, as well as the fucosylation of therapeutic antibodies or the manipulation of fucosylation and their implications as new therapeutic modalities for cancer.
岩藻糖是一种膳食糖，细胞在糖基化过程中使用它来对蛋白质的行为和功能进行翻译后修饰和调节。由于糖基化在正常器官和免疫发育及稳态中发挥着重要的细胞功能，因此在许多病理生理情况下发现它受到干扰也就不足为奇了，包括癌症。多年来越来越多的研究强调了糖基化改变在肿瘤细胞内在和旁分泌信号转导和相互作用中可以发挥的关键作用。特别是，研究表明糖基化会影响肿瘤：免疫相互作用，并显著增强或减弱抗肿瘤免疫。重要的是，糖基化似乎是一种可以通过治疗靶向的翻译后修饰，因为操纵糖基化的分子基础已被证明足以损害或阻断肿瘤进展并调节抗肿瘤免疫。此外，抗癌药物（如治疗性抗体）的糖基化已被证明会极大地影响其疗效。在这篇综述中，我们总结了糖基化在癌症和免疫细胞中未被充分认识的作用，以及治疗性抗体的糖基化或糖基化的操纵及其作为癌症新治疗方式的意义。
