Autotaxin and lysophosphatidic acid stimulate intestinal cell motility by redistribution of the actin modifying protein villin to the developing lamellipodia

Seema Khurana, Alok Tomar, Sudeep P. George, Yaohong Wang, Mohammad Rizwan Siddiqui, Huazhang Guo, Gabor Tigyi, Sijo Mathew

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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-γ1. Together, our results show that in epithelial cells ATX and LPA act as strong stimulators of cell migration by recruiting PLC-γ1 and villin, both of which participate in the initiation of protrusion.

Original languageEnglish (US)
Pages (from-to)530-542
Number of pages13
JournalExperimental Cell Research
Volume314
Issue number3
DOIs
StatePublished - Feb 1 2008

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Pseudopodia
Gastrointestinal Motility
Cell Movement
Actins
Proteins
Lysophosphatidic Acid Receptors
Epithelial Cells
Lysophosphatidylcholines
lysophosphatidic acid
villin
Pertussis Toxin
Colonic Neoplasms
Intestines
Neoplasms
Phosphorylation
Kidney
Lipids
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Cell Biology

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Autotaxin and lysophosphatidic acid stimulate intestinal cell motility by redistribution of the actin modifying protein villin to the developing lamellipodia. / Khurana, Seema; Tomar, Alok; George, Sudeep P.; Wang, Yaohong; Siddiqui, Mohammad Rizwan; Guo, Huazhang; Tigyi, Gabor; Mathew, Sijo.

In: Experimental Cell Research, Vol. 314, No. 3, 01.02.2008, p. 530-542.

Research output: Contribution to journalArticle

Khurana, Seema ; Tomar, Alok ; George, Sudeep P. ; Wang, Yaohong ; Siddiqui, Mohammad Rizwan ; Guo, Huazhang ; Tigyi, Gabor ; Mathew, Sijo. / Autotaxin and lysophosphatidic acid stimulate intestinal cell motility by redistribution of the actin modifying protein villin to the developing lamellipodia. In: Experimental Cell Research. 2008 ; Vol. 314, No. 3. pp. 530-542.
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