美国哈佛医学院Peter K. Sorger等研究人员合作发现，CRISPRi/a筛选平台可用于研究不同微环境中的细胞营养运输 。这一研究成果于2024年4月11日在线发表在国际学术期刊《自然—细胞生物学》上。

研究人员报告了一种CRISPR干扰/激活筛选平台，该平台可系统地检测营养物质转运体对支持癌细胞，在从标准培养基到肿瘤等各种环境中增殖的贡献。研究人员应用该平台鉴定了白血病细胞中的氨基酸转运体，发现氨基酸转运涉及依赖于微环境组成的高双向通量。在研究转运体在胱氨酸饥饿细胞中的作用时，研究人员发现了血清素摄取在防止铁死亡中的作用。

最后，研究人员确定了皮下肿瘤细胞增殖所必需的转运体，并发现葡萄糖和氨基酸的水平可抑制该环境中的细胞增殖。这项研究建立了一个框架，可用于系统识别关键的细胞营养转运体，描述它们的功能，并探索肿瘤微环境如何影响癌症代谢。

据悉，阻断癌细胞增殖所必需的营养物质的输入是一个治疗机会，但目前还不清楚要针对哪些转运体。

附：英文原文

Title: A CRISPRi/a screening platform to study cellular nutrient transport in diverse microenvironments

Author: Chidley, Christopher, Darnell, Alicia M., Gaudio, Benjamin L., Lien, Evan C., Barbeau, Anna M., Vander Heiden, Matthew G., Sorger, Peter K.

Issue&Volume: 2024-04-11

Abstract: Blocking the import of nutrients essential for cancer cell proliferation represents a therapeutic opportunity, but it is unclear which transporters to target. Here we report a CRISPR interference/activation screening platform to systematically interrogate the contribution of nutrient transporters to support cancer cell proliferation in environments ranging from standard culture media to tumours. We applied this platform to identify the transporters of amino acids in leukaemia cells and found that amino acid transport involves high bidirectional flux dependent on the microenvironment composition. While investigating the role of transporters in cystine starved cells, we uncovered a role for serotonin uptake in preventing ferroptosis. Finally, we identified transporters essential for cell proliferation in subcutaneous tumours and found that levels of glucose and amino acids can restrain proliferation in that environment. This study establishes a framework for systematically identifying critical cellular nutrient transporters, characterizing their function and exploring how the tumour microenvironment impacts cancer metabolism.

DOI: 10.1038/s41556-024-01402-1

Source: https://www.nature.com/articles/s41556-024-01402-1