ArticleThe Journal of biological chemistry2013
FOXO3 growth inhibition of colonic cells is dependent on intraepithelial lipid droplet density.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 63 citations in OpenAlex.
- Activation of a FOXO3-induced cell cycle arrest regulates ferroptosis.Cell death discovery · 2025Article
- Lipids: Driving Forces in the Underlying Biology of Carcinogenesis.ACS pharmacology & translational science · 2025Review
- CAMKIIδ Reinforces Lipid Metabolism and Promotes the Development of B Cell Lymphoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Regulating Lipid MetabolismRecent patents on anti-cancer drug discovery · 2025Article
- FOXO3: at the crossroads of metabolic, inflammatory, and tumorigenic remodeling in the colon.American journal of physiology. Gastrointestinal and liver physiology · 2024Review
- Are lipid droplets the picnic basket of brain tumours?Cell death discovery · 2024Review
- Challenges in Pharmacological Intervention in Perilipins (PLINs) to Modulate Lipid Droplet Dynamics in Obesity and Cancer.Cancers · 2023Review
- FOXO3 Deficiency in Neutrophils Drives Colonic Inflammation and Tumorigenesis.International journal of molecular sciences · 2023Article
- Article
- Lipid Metabolism in Glioblastoma: From De Novo Synthesis to Storage.Biomedicines · 2022Review
- FOXO3 Expression in Macrophages Is Lowered by a High-Fat Diet and Regulates Colonic Inflammation and Tumorigenesis.Metabolites · 2022Article
- Elevated ATGL in colon cancer cells and cancer stem cells promotes metabolic and tumorigenic reprogramming reinforced by obesity.Oncogenesis · 2021Article
- When Activator and Inhibitor of PPARα Do the Same: Consequence for Differentiation of Human Intestinal Cells.Biomedicines · 2021Article
- Sirtuin 6 regulates the proliferation and survival of clear cell renal cell carcinoma cells via B-cell lymphoma 2.Oncology letters · 2021Article
- Lipid Metabolism in Cancer Cells.Advances in experimental medicine and biology · 2021Article
- Gut microbes effects on host metabolic alterations in health and disease.Gut microbes · 2020Article
- Lipid droplets: platforms with multiple functions in cancer hallmarks.Cell death & disease · 2020Review
- Lipid droplet and its implication in cancer progression.American journal of cancer research · 2020Review
- PLIN2 Functions As a Novel Link Between Progesterone Signaling and Metabolism in Uterine Leiomyoma Cells.The Journal of clinical endocrinology and metabolism · 2019Article
- Lipid droplet velocity is a microenvironmental sensor of aggressive tumors regulated by V-ATPase and PEDF.Laboratory investigation; a journal of technical methods and pathology · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Forkhead transcription factor FOXO3 plays a critical role in suppressing tumor growth, in part, by increasing the cell cycle inhibitor p27kip1, and Foxo3 deficiency in mice results in marked colonic epithelial proliferation. Here, we show in Foxo3-deficient colonic epithelial cells a striking increase in intracytoplasmic lipid droplets (LDs), a dynamic organelle recently observed in human tumor tissue. Although the regulation and function of LDs in non-adipocytes is unclear, we hypothesize that the anti-proliferative effect of FOXO3 was dependent on lowering LD density, thus decreasing fuel energy in both normal and colon cancer cells. In mouse colonic tumors, we found an increased expression of LD coat protein PLIN2 compared with normal colonic epithelial cells. Stimulation of LD density in human colon cancer cells led to a PI3K-dependent loss of FOXO3 and a decrease in the negative regulator of lipid metabolism in Sirtuin6 (SIRT6). Foxo3 deficiency also led to a decrease in SIRT6, revealing the existence of LD and FOXO3 feedback regulation in colonic cells. In parallel, LD-dependent loss of FOXO3 led to its dissociation from the promoter and decreased expression of the cell cycle inhibitor p27kip1. Stimulation of LD density promoted proliferation in colon cancer cells, whereas silencing PLIN2 or overexpression of FOXO3 inhibited proliferation. Taken together, FOXO3 and LDs might serve as new targets for therapeutic intervention of colon cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.