ArticleThe Journal of biological chemistry2014
Rho GTPases RhoA and Rac1 mediate effects of dietary folate on metastatic potential of A549 cancer cells through the control of cofilin phosphorylation.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 51 citations in OpenAlex.
- The Cellular and Mitochondrial Consequences of Mevalonate Pathway Inhibition by Nitrogen-Containing Bisphosphonates: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Protective Effect of myo-Inositol Against Decitabine-Induced Neural Tube Defects in Embryonic Zebrafish.Neurotoxicity research · 2025Article
- Therapeutic targeting of voltage-gated sodium channel NaFrontiers in pharmacology · 2024Review
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- Folylpolyglutamate synthetase mRNA G-quadruplexes regulate its cell protrusion localization and enhance a cancer cell invasive phenotype upon folate repletion.BMC biology · 2023Article
- ERK3 and DGKζ interact to modulate cell motility in lung cancer cells.Frontiers in cell and developmental biology · 2023Article
- Article
- Folic acid depletion as well as oversupplementation helps in the progression of hepatocarcinogenesis in HepG2 cells.Scientific reports · 2022Article
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- FMNL2 suppresses cell migration and invasion of breast cancer: a reduction of cytoplasmic p27 via RhoA/LIMK/Cofilin pathway.Cell death discovery · 2022Article
- Ceramide synthase 6 mediates sex-specific metabolic response to dietary folic acid in mice.The Journal of nutritional biochemistry · 2021Article
- Designing Relevant Preclinical Rodent Models for Studying Links Between Nutrition, Obesity, Metabolism, and Cancer.Annual review of nutrition · 2021Review
- Hhex inhibits cell migration via regulating RHOA/CDC42-CFL1 axis in human lung cancer cells.Cell communication and signaling : CCS · 2021Article
- Syndecan-4 in Tumor Cell Motility.Cancers · 2021Review
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- Myo-Inositol as a Key Supporter of Fertility and Physiological Gestation.Pharmaceuticals (Basel, Switzerland) · 2021Review
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- Article
- Elevated Expression of Gamma-Glutamyl Hydrolase Is Associated With Poor Prognosis and Altered Immune Signature in Uterine Corpus Endometrial Carcinoma.Frontiers in genetics · 2021Article
- Aldh1l2 knockout mouse metabolomics links the loss of the mitochondrial folate enzyme to deregulation of a lipid metabolism observed in rare human disorder.Human genomics · 2020Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Folate, an important nutrient in the human diet, has been implicated in cancer, but its role in metastasis is not established. We have shown previously that the withdrawal of medium folate leads to the inhibition of migration and invasion of A549 lung carcinoma cells. Here we have demonstrated that medium folate regulates the function of Rho GTPases by enabling their carboxyl methylation and translocation to plasma membrane. Conversely, the lack of folate leads to the retention of these proteins in endoplasmic reticulum. Folate also promoted the switch from inactive (GDP-bound) to active (GTP-bound) GTPases, resulting in the activation of downstream kinases p21-activated kinase and LIM kinase and phosphorylation of the actin-depolymerizing factor cofilin. We have further demonstrated that in A549 cells two GTPases, RhoA and Rac1, but not Cdc42, are immediate sensors of folate status: the siRNA silencing of RhoA or Rac1 blocked effects of folate on cofilin phosphorylation and cellular migration and invasion. The finding that folate modulates metastatic potential of cancer cells was confirmed in an animal model of lung cancer using tail vein injection of A549 cells in SCID mice. A folate-rich diet enhanced lung colonization and distant metastasis to lymph nodes and decreased overall survival (35 versus 63 days for mice on a folate-restricted diet). High folate also promoted epithelial-mesenchymal transition in cancer cells and experimental mouse tumors. Our study provides experimental evidence for a mechanism of metastasis promotion by dietary folate and highlights the interaction between nutrients and metastasis-related signaling.
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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.