Document Detail


Autotaxin and lysophosphatidic acid stimulate intestinal cell motility by redistribution of the actin modifying protein villin to the developing lamellipodia.
MedLine Citation:
PMID:  18054784     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Seema Khurana; Alok Tomar; Sudeep P George; Yaohong Wang; Mohammad Rizwan Siddiqui; Huazhang Guo; Gabor Tigyi; Sijo Mathew
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-11-12
Journal Detail:
Title:  Experimental cell research     Volume:  314     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-24     Completed Date:  2008-04-14     Revised Date:  2011-11-07    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  530-42     Citation Subset:  IM    
Affiliation:
Department of Physiology, University of Tennessee Health Science Center Memphis, TN 38163, USA. skhurana@utmem.edu <skhurana@utmem.edu>
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MeSH Terms
Descriptor/Qualifier:
Actins / 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:
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:
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

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