ArticleThe Journal of biological chemistry2007
Lysophosphatidic acid facilitates proliferation of colon cancer cells via induction of Krüppel-like factor 5.
Article in The Journal of biological chemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Discovery of common and rare genetic risk variants for colorectal cancer.Nature genetics · 2019Pooled it
- LPAAmerican journal of physiology. Gastrointestinal and liver physiology · 2024Article
- New insights into KLFs and SOXs in cancer pathogenesis, stemness, and therapy.Seminars in cancer biology · 2023Review
- Lysophosphatidic Acid Promotes Epithelial-Mesenchymal Transition in Kidney Epithelial Cells via the LPAR1/MAPK-AKT/KLF5 Signaling Pathway in Diabetic Nephropathy.International journal of molecular sciences · 2022Article
- Compensatory Upregulation of LPACells · 2022Article
- Inhibition of ChREBP ubiquitination via the ROS/Akt-dependent downregulation of Smurf2 contributes to lysophosphatidic acid-induced fibrosis in renal mesangial cells.Journal of biomedical science · 2022Article
- Krüppel-like factor (KLF)5: An emerging foe of cardiovascular health.Journal of molecular and cellular cardiology · 2022Review
- Review
- Fat of the Gut: Epithelial Phospholipids in Inflammatory Bowel Diseases.International journal of molecular sciences · 2021Review
- Progress in the Development of Eukaryotic Elongation Factor 2 Kinase (eEF2K) Natural Product and Synthetic Small Molecule Inhibitors for Cancer Chemotherapy.International journal of molecular sciences · 2021Review
- A Forgotten Corner in Cancer Immunotherapy: The Role of Lipids.Frontiers in oncology · 2021Review
- The Novel Small-Molecule SR18662 Efficiently Inhibits the Growth of Colorectal CancerMolecular cancer therapeutics · 2019Article
- Lysophosphatidic Acid and Autotaxin-associated Effects on the Initiation and Progression of Colorectal Cancer.Cancers · 2019Review
- Autotaxin determines colitis severity in mice and is secreted by B cells in the colon.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Lysophosphatidic acid increases mesangial cell proliferation in models of diabetic nephropathy via Rac1/MAPK/KLF5 signaling.Experimental & molecular medicine · 2019Article
- The role of CCN4/WISP-1 in the cancerous phenotype.Cancer management and research · 2018Review
- Lysophosphatidic Acid Is Associated With Cardiac Dysfunction and Hypertrophy by Suppressing Autophagy via the LPA3/AKT/mTOR Pathway.Frontiers in physiology · 2018Article
- Group III phospholipase AScientific reports · 2017Article
- SP and KLF Transcription Factors in Digestive Physiology and Diseases.Gastroenterology · 2017Review
- G Protein-Coupled Receptors in Cancer.International journal of molecular sciences · 2016Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Among the multiple cellular effects mediated by lysophosphatidic acid (LPA), the effect on cell proliferation has extensively been investigated. A recent study showed that LPA-mediated proliferation of colon cancer cells requires activation of beta-catenin. However, the majority of colon cancer cells have deregulation of the Wnt/beta-catenin pathway. This prompted us to hypothesize the presence of additional pathway(s) activated by LPA resulting in an increase in the proliferation of colon cancer cells. Krüppel-like factor 5 (KLF5) is a transcriptional factor highly expressed in the crypt compartment of the intestinal epithelium. In this work, we investigated a role of KLF5 in LPA-mediated proliferation. We show that LPA stimulated the expression levels of KLF5 mRNA and protein in colon cancer cells and this stimulation was mediated by LPA(2) and LPA(3). Silencing of KLF5 expression by small interfering RNA significantly attenuated LPA-mediated proliferation of SW480 and HCT116 cells. LPA-mediated KLF5 induction was partially blocked by inhibition of the mitogen-activated protein kinase kinase and protein kinase C-delta. Moreover, we observed that LPA regulates KLF5 expression via eukaryotic elongation factor 2 kinase (eEF2k). Inhibition of calmodulin or silencing of eEF2k blocked the stimulation in KLF5 expression. Knockdown of eEF2k specifically inhibited KLF5 induction by LPA but not by fetal bovine serum or phorbol 12-myristate 13-acetate. These results identify KLF5 as a target of LPA-mediated signaling and suggest a role of KLF5 in promoting proliferation of intestinal epithelia in response to LPA.
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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.