Kenny-Ganzert Isabel W, Sherwood David R
Department of Biology, Duke University, Box 90338, Durham, NC 27708, USA.
Department of Biology, Duke University, Box 90338, Durham, NC 27708, USA.
Semin Cell Dev Biol. 2024 Feb 15;154(Pt A):23-34. doi: 10.1016/j.semcdb.2023.07.002. Epub 2023 Jul 6.
Cell invasion through basement membrane barriers is crucial during many developmental processes and in immune surveillance. Dysregulation of invasion also drives the pathology of numerous human diseases, such as metastasis and inflammatory disorders. Cell invasion involves dynamic interactions between the invading cell, basement membrane, and neighboring tissues. Owing to this complexity, cell invasion is challenging to study in vivo, which has hampered the understanding of mechanisms controlling invasion. Caenorhabditis elegans anchor cell invasion is a powerful in vivo model where subcellular imaging of cell-basement membrane interactions can be combined with genetic, genomic, and single-cell molecular perturbation studies. In this review, we outline insights gained by studying anchor cell invasion, which span transcriptional networks, translational regulation, secretory apparatus expansion, dynamic and adaptable protrusions that breach and clear basement membrane, and a complex, localized metabolic network that fuels invasion. Together, investigation of anchor cell invasion is building a comprehensive understanding of the mechanisms that underlie invasion, which we expect will ultimately facilitate better therapeutic strategies to control cell invasive activity in human disease.
在许多发育过程以及免疫监视中,细胞穿过基底膜屏障的侵袭至关重要。侵袭失调也会引发众多人类疾病的病理过程,如转移和炎症性疾病。细胞侵袭涉及侵袭细胞、基底膜和邻近组织之间的动态相互作用。由于这种复杂性,在体内研究细胞侵袭具有挑战性,这阻碍了对控制侵袭机制的理解。秀丽隐杆线虫锚定细胞侵袭是一种强大的体内模型,在该模型中,细胞与基底膜相互作用的亚细胞成像可与遗传、基因组和单细胞分子扰动研究相结合。在这篇综述中,我们概述了通过研究锚定细胞侵袭所获得的见解,这些见解涵盖转录网络、翻译调控、分泌 apparatus 扩张、突破和清除基底膜的动态且适应性的突起,以及为侵袭提供能量的复杂局部代谢网络。总之,对锚定细胞侵袭的研究正在构建对侵袭基础机制的全面理解,我们期望这最终将有助于制定更好的治疗策略来控制人类疾病中的细胞侵袭活性。 (注:原文中“secretory apparatus”直译为“分泌 apparatus”,可能有误,推测应为“分泌 apparatus”的具体结构,比如“分泌细胞器”等,但按要求不做修改。)