稳态与癌症中的肠道干细胞动力学

Intestinal stem cell dynamics in homeostasis and cancer.

作者信息

Ramadan Rana, van Driel Milou S, Vermeulen Louis, van Neerven Sanne M

机构信息

Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands; Oncode Institute, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

出版信息

Trends Cancer. 2022 May;8(5):416-425. doi: 10.1016/j.trecan.2022.01.011. Epub 2022 Feb 10.

DOI:10.1016/j.trecan.2022.01.011

PMID:35153158

Abstract

The relationship between intestinal stem cells (ISCs) and colorectal cancer (CRC) has been a topic of intense study. Uncovering stem cell dynamics in homeostasis and following acquisition of oncogenic mutations has provided unprecedented insights into CRC initiation, and it is increasingly evident that the microenvironment plays a key role in regulating stem cell fate and functionality. Consequently, imbalances in the signaling between the niche and ISCs perturb homeostasis and promote cancer development. Furthermore, stem cell-like cells drive growth and progression of established CRCs and these cells also critically rely on microenvironmental input. Here, we highlight the importance of stem cell/niche interactions in developing and established CRC and discuss how these can be modulated to develop novel preventive and therapeutic interventions.

摘要

肠道干细胞（ISCs）与结直肠癌（CRC）之间的关系一直是深入研究的课题。揭示稳态下以及获得致癌突变后的干细胞动态变化，为CRC的起始提供了前所未有的见解，并且越来越明显的是，微环境在调节干细胞命运和功能方面起着关键作用。因此，生态位与ISCs之间信号传导的失衡会扰乱稳态并促进癌症发展。此外，干细胞样细胞驱动已形成的CRC的生长和进展，并且这些细胞也严重依赖微环境输入。在此，我们强调干细胞/生态位相互作用在CRC发生发展过程中的重要性，并讨论如何调节这些相互作用以开发新的预防和治疗干预措施。