| Autotaxin and lysophosphatidic acid stimulate intestinal cell motility by redistribution of the actin modifying protein villin to the developing lamellipodia. | |
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MedLine Citation:
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PMID: 18054784 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Autotaxin (ATX) is a potent tumor cell motogen that can produce lysophosphatidic acid (LPA) from lysophosphatidylcholine. LPA is a lipid mediator that has also been shown to modulate tumor cell invasion. Autotaxin mRNA is expressed at significant levels in the intestine. Likewise, LPA2 receptor levels have been shown to be elevated in colon cancers. The molecular mechanism of ATX/LPA-induced increase in intestinal cell migration however, remains poorly understood. Villin is an intestinal and renal epithelial cell specific actin regulatory protein that modifies epithelial cell migration. In this study we demonstrate that both Caco-2 (endogenous villin) and MDCK (exogenous villin) cells, which express primarily LPA2 receptors, show enhanced cell migration in response to ATX/LPA. ATX and LPA treatment results in the rapid formation of lamellipodia and redistribution of villin to these cell surface structures, suggesting a role for villin in regulating this initial event of cell locomotion. The LPA-induced increase in cell migration required activation of c-src kinase and downstream tyrosine phosphorylation of villin by c-src kinase. LPA stimulated cell motility was determined to be insensitive to pertussis toxin, but was regulated by activation of PLC-gamma 1. Together, our results show that in epithelial cells ATX and LPA act as strong stimulators of cell migration by recruiting PLC-gamma 1 and villin, both of which participate in the initiation of protrusion. |
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Authors:
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Seema Khurana; Alok Tomar; Sudeep P George; Yaohong Wang; Mohammad Rizwan Siddiqui; Huazhang Guo; Gabor Tigyi; Sijo Mathew |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2007-11-12 |
Journal Detail:
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Title: Experimental cell research Volume: 314 ISSN: 0014-4827 ISO Abbreviation: Exp. Cell Res. Publication Date: 2008 Feb |
Date Detail:
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Created Date: 2008-01-24 Completed Date: 2008-04-14 Revised Date: 2011-11-07 |
Medline Journal Info:
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Nlm Unique ID: 0373226 Medline TA: Exp Cell Res Country: United States |
Other Details:
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Languages: eng Pagination: 530-42 Citation Subset: IM |
Affiliation:
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Department of Physiology, University of Tennessee Health Science Center Memphis, TN 38163, USA. skhurana@utmem.edu <skhurana@utmem.edu> |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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metabolism Animals Caco-2 Cells Carcinoma / metabolism Cell Line Cell Movement / drug effects, physiology* Dogs Humans Intestinal Mucosa / cytology, drug effects, metabolism* Intestinal Neoplasms / metabolism Lysophospholipids / pharmacology, physiology* Microfilament Proteins / drug effects, metabolism*, pharmacology Multienzyme Complexes / pharmacology, physiology* Phosphodiesterase I / pharmacology, physiology* Phospholipase C gamma / drug effects, metabolism Phosphorylation / drug effects Protein Transport / drug effects, physiology Pseudopodia / drug effects, metabolism*, ultrastructure Pyrophosphatases / pharmacology, physiology* Receptors, Lysophosphatidic Acid / drug effects, metabolism src-Family Kinases / drug effects, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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CA-92160/CA/NCI NIH HHS; DK-54755/DK/NIDDK NIH HHS; DK-65006/DK/NIDDK NIH HHS; R01 DK054755-09/DK/NIDDK NIH HHS; R01 DK065006-04/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/Lysophospholipids; 0/Microfilament Proteins; 0/Multienzyme Complexes; 0/Receptors, Lysophosphatidic Acid; 0/villin; 22002-87-5/lysophosphatidic acid; EC 2.7.10.2/src-Family Kinases; EC 3.1.4.1/Phosphodiesterase I; EC 3.1.4.3/Phospholipase C gamma; EC 3.1.4.39/alkylglycerophosphoethanolamine phosphodiesterase; EC 3.6.1.-/Pyrophosphatases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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