Academic Journal
A CRISPRi/a screening platform to study cellular nutrient transport in diverse microenvironments
| العنوان: | A CRISPRi/a screening platform to study cellular nutrient transport in diverse microenvironments |
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| المؤلفون: | Chidley, Christopher, Darnell, Alicia M., Gaudio, Benjamin L., Lien, Evan C., Barbeau, Anna M., Vander Heiden, Matthew G., Sorger, Peter K. |
| المساهمون: | Jane Coffin Childs Memorial Fund for Medical Research, U.S. Department of Health & Human Services | NIH | National Cancer Institute, Lustgarten Foundation, Ludwig Institute for Cancer Research, MIT Center for Precision Cancer Medicine, Termeer Foundation |
| المصدر: | Nature Cell Biology ; volume 26, issue 5, page 825-838 ; ISSN 1465-7392 1476-4679 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2024 |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41556-024-01402-1 |
| الاتاحة: | http://dx.doi.org/10.1038/s41556-024-01402-1 https://www.nature.com/articles/s41556-024-01402-1.pdf https://www.nature.com/articles/s41556-024-01402-1 |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.B8BEB933 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41556-024-01402-1 |
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