The DOI matches its Crossref record; 82 of the 82 references it cites were found in a registry or an index.
Dysregulated cholesterol homeostasis results in resistance to ferroptosis increasing tumorigenicity and metastasis in cancer
Open accessAbstract
Hypercholesterolemia and dyslipidemia are associated with an increased risk for many cancer types and with poor outcomes in patients with established disease. Whereas the mechanisms by which this occurs are multifactorial we determine that chronic exposure of cells to 27-hydroxycholesterol (27HC), an abundant circulating cholesterol metabolite, selects for cells that exhibit increased cellular uptake and/or lipid biosynthesis. These cells exhibit substantially increased tumorigenic and metastatic capacity. Notably, the metabolic stress imposed upon cells by the accumulated lipids requires sustained expression of GPX4, a negative regulator of ferroptotic cell death. We show that resistance to ferroptosis is a feature of metastatic cells and further demonstrate that GPX4 knockdown attenuates the enhanced tumorigenic and metastatic activity of 27HC resistant cells. These findings highlight the general importance of ferroptosis in tumor growth and metastasis and suggest that dyslipidemia/hypercholesterolemia impacts cancer pathogenesis by selecting for cells that are resistant to ferroptotic cell death.
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Cites
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Cited by
Targeting Ferroptosis as a Vulnerability in Cancer
Lei, G., Zhuang, L., & Gan, B. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00459-0 · Cited by 2,252
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The role of lipid metabolic reprogramming in tumor microenvironment
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The Role of Iron in Cancer Progression
Guo, Q., Li, L., Hou, S., Yuan, Z., Li, C., Zhang, W., Zheng, L., & Li, X. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.778492 · Cited by 150
Metadata
- Authors
- Liu, W., Chakraborty, B., Safi, R., Kazmin, D., Chang, C.-Y., & McDonnell, D. P.
- Venue
- Nature Communications
- Published
- 2021-08-24
- Volume
- 12
- Issue
- 1
- Pages
- 5103-5103
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W3194627617
- Cited by
- 341
- References
- 82
- FWCI
- 29.22
- Type
- journal article
- Language
- en
- Open access
- gold
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- Liu, W., Chakraborty, B., Safi, R., Kazmin, D., Chang, C.-Y., & McDonnell, D. P. (2021). Dysregulated cholesterol homeostasis results in resistance to ferroptosis increasing tumorigenicity and metastasis in cancer. Nature Communications. https://doi.org/10.1038/s41467-021-25354-4
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