The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Phospholipid Remodeling and Cholesterol Availability Regulate Intestinal Stemness and Tumorigenesis
Open accessAbstract
Summary Adequate availability of cellular building blocks, including lipids, is a prerequisite for cellular proliferation, but excess dietary lipids are linked to increased cancer risk. Despite these connections, specific regulatory relationships between membrane composition, intestinal stem cell (ISC) proliferation and tumorigenesis are unclear. We reveal an unexpected link between membrane phospholipid remodeling and cholesterol biosynthesis and demonstrate that cholesterol itself acts as a mitogen for ISCs. Inhibition of the phospholipid-remodeling enzyme Lpcat3 increases membrane saturation and stimulates cholesterol biosynthesis, thereby driving ISC proliferation. Pharmacologic inhibition of cholesterol synthesis normalizes crypt hyperproliferation in Lpcat3-deficient organoids and mice. Conversely, increasing cellular cholesterol content stimulates crypt organoid growth, and providing excess dietary cholesterol or driving endogenous cholesterol synthesis through SREBP-2 expression promotes ISC proliferation in vivo. Finally, disruption of Lpcat3-dependent phospholipid and cholesterol homeostasis dramatically enhances tumor formation in Apcmin mice. These findings identify a critical dietary-responsive phospholipid-cholesterol axis regulating ISC proliferation and tumorigenesis.
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SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth
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Cited by
Greasing the Wheels of the Cancer Machine: The Role of Lipid Metabolism in Cancer
Snaebjornsson, M. T., Janaki-Raman, S., & Schulze, A. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2019.11.010 · Cited by 1,097
Liver X receptors in lipid signalling and membrane homeostasis
Wang, B., & Tontonoz, P. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0037-x · Cited by 722
Self-citationPhospholipid Remodeling in Physiology and Disease
Wang, B., & Tontonoz, P. (2019) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020518-114444 · Cited by 527
Self-citationMihaylova, M. M., Cheng, C.-W., Cao, A. Q., Tripathi, S., Mana, M. D., Bauer-Rowe, K. E., Abu-Remaileh, M., Clavain, L., Erdemir, A., Lewis, C. A., et al. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.04.001 · Cited by 428
Metabolic Pathways Regulating Colorectal Cancer Initiation and Progression
La Vecchia, S., & Sebastián, C. (2020) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2019.05.018 · Cited by 349
Metadata
- Authors
- Wang, B., Rong, X., Palladino, E. N. D., Wang, J., Fogelman, A. M., Martín, M. G., Alrefai, W. A., Ford, D. A., & Tontonoz, P.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 22
- Issue
- 2
- Pages
- 206-220.e4
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2784611114
- Cited by
- 317
- References
- 58
- FWCI
- 9.55
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Wang, B., Rong, X., Palladino, E. N. D., Wang, J., Fogelman, A. M., Martín, M. G., Alrefai, W. A., Ford, D. A., & Tontonoz, P. (2018). Phospholipid Remodeling and Cholesterol Availability Regulate Intestinal Stemness and Tumorigenesis. Cell Stem Cell. https://doi.org/10.1016/j.stem.2017.12.017
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