spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
JCS ePress online publication date 5 Aug 2003
doi: 10.1242/jcs.00679

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jcs.00679v1
116/18/3835    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stähle, M.
Right arrow Articles by Giehl, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stähle, M.
Right arrow Articles by Giehl, K.

Research Article

Mechanisms in LPA-induced tumor cell migration: critical role of phosphorylated ERK


Martina Stähle, Christine Veit, Ulla Bachfischer, Karina Schierling, Bettina Skripczynski, Alan Hall, Peter Gierschik, and Klaudia Giehl*
* Author for correspondence (e-mail: klaudia.giehl{at}medizin.uni-ulm.de)

Lysophosphatidic acid (LPA) is a serum-borne phospholipid with hormone and growth factor-like properties. LPA has been shown to modulate tumor cell invasion and malignant cell growth. Here, we report that two human pancreatic carcinoma cell lines, PANC-1 and BxPC-3, express functionally active LPA receptors coupled to pertussis toxin-sensitive Gi/o-proteins. In contrast to other cell types, LPA does not act as a mitogen, but is an efficacious stimulator of cell migration of these tumor cells. LPA-induced chemotaxis is markedly dependent on activation of PTX-sensitive heterotrimeric G-proteins, on activation of the small GTPases Ras, Rac and RhoA, and on GTPase-dependent activation of ERK. LPA-induced ERK activation results in a transient translocation of the phosphorylated ERK to newly forming focal contact sites at the leading edge of the migrating cells. Inhibition of ERK activation and its subsequent translocation impaired LPA-induced chemotaxis and LPA-induced actin reorganization. Thus, pancreatic tumor cell migration in response to LPA is essentially controlled by activation of a Gi/o-ERK pathway and requires the LPA-induced activation of Ras, Rac1 and RhoA.


This article has been cited by other articles:


Home page
 Cancer Res.Home page
K. Lange, M. Kammerer, F. Saupe, M. E. Hegi, S. Grotegut, E. Fluri, and G. Orend
Combined Lysophosphatidic Acid/Platelet-Derived Growth Factor Signaling Triggers Glioma Cell Migration in a Tenascin-C Microenvironment
Cancer Res., September 1, 2008; 68(17): 6942 - 6952.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Liu, X. Fang, H. Hall, S. Yu, D. Smith, Z. Lu, D. Fang, J. Liu, L. C. Stephens, J. R. Woodgett, et al.
Homozygous deletion of glycogen synthase kinase 3{beta} bypasses senescence allowing Ras transformation of primary murine fibroblasts
PNAS, April 1, 2008; 105(13): 5248 - 5253.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
K. Giehl, A. Graness, and M. Goppelt-Struebe
The small GTPase Rac-1 is a regulator of mesangial cell morphology and thrombospondin-1 expression
Am J Physiol Renal Physiol, February 1, 2008; 294(2): F407 - F413.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
S. Muehlich, I. Cicha, C. D. Garlichs, B. Krueger, G. Posern, and M. Goppelt-Struebe
Actin-dependent regulation of connective tissue growth factor
Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1732 - C1738.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. M. F. Liu, R. K. H. Lo, C. S. S. Wong, C. Morris, H. Wise, and Y. H. Wong
Activation of STAT3 by G{alpha}s Distinctively Requires Protein Kinase A, JNK, and Phosphatidylinositol 3-Kinase
J. Biol. Chem., November 24, 2006; 281(47): 35812 - 35825.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
A. W. Jehle, S. J. Gardai, S. Li, P. Linsel-Nitschke, K. Morimoto, W. J. Janssen, R. W. Vandivier, N. Wang, S. Greenberg, B. M. Dale, et al.
ATP-binding cassette transporter A7 enhances phagocytosis of apoptotic cells and associated ERK signaling in macrophages
J. Cell Biol., August 14, 2006; 174(4): 547 - 556.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
X. Cui, H.-J. Kim, I. Kuiatse, H. Kim, P. H. Brown, and A. V. Lee
Epidermal Growth Factor Induces Insulin Receptor Substrate-2 in Breast Cancer Cells via c-Jun NH2-Terminal Kinase/Activator Protein-1 Signaling to Regulate Cell Migration.
Cancer Res., May 15, 2006; 66(10): 5304 - 5313.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
C. E. Pullar, J. C. Grahn, W. Liu, and R. R. Isseroff
{beta}2-Adrenergic receptor activation delays wound healing
FASEB J, January 1, 2006; 20(1): 76 - 86.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y.-J. Lai, C.-S. Chen, W.-C. Lin, and F.-T. Lin
c-Src-Mediated Phosphorylation of TRIP6 Regulates Its Function in Lysophosphatidic Acid-Induced Cell Migration
Mol. Cell. Biol., July 15, 2005; 25(14): 5859 - 5868.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
A. Pullikuth, E. McKinnon, H.-J. Schaeffer, and A. D. Catling
The MEK1 Scaffolding Protein MP1 Regulates Cell Spreading by Integrating PAK1 and Rho Signals
Mol. Cell. Biol., June 15, 2005; 25(12): 5119 - 5133.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
T. Maffucci, F. T. Cooke, F. M. Foster, C. J. Traer, M. J. Fry, and M. Falasca
Class II phosphoinositide 3-kinase defines a novel signaling pathway in cell migration
J. Cell Biol., June 6, 2005; 169(5): 789 - 799.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
D. L. Hunton, W. G. Barnes, J. Kim, X.-R. Ren, J. D. Violin, E. Reiter, G. Milligan, D. D. Patel, and R. J. Lefkowitz
{beta}-Arrestin 2-Dependent Angiotensin II Type 1A Receptor-Mediated Pathway of Chemotaxis
Mol. Pharmacol., April 1, 2005; 67(4): 1229 - 1236.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
L. V. Yang, C. G. Radu, L. Wang, M. Riedinger, and O. N. Witte
Gi-independent macrophage chemotaxis to lysophosphatidylcholine via the immunoregulatory GPCR G2A
Blood, February 1, 2005; 105(3): 1127 - 1134.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Veit, F. Genze, A. Menke, S. Hoeffert, T. M. Gress, P. Gierschik, and K. Giehl
Activation of Phosphatidylinositol 3-Kinase and Extracellular Signal-Regulated Kinase Is Required for Glial Cell Line-Derived Neurotrophic Factor-Induced Migration and Invasion of Pancreatic Carcinoma Cells
Cancer Res., August 1, 2004; 64(15): 5291 - 5300.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. Bian, S. Su, C. Mahanivong, R. K. Cheng, Q. Han, Z. K. Pan, P. Sun, and S. Huang
Lysophosphatidic Acid Stimulates Ovarian Cancer Cell Migration via a Ras-MEK Kinase 1 Pathway
Cancer Res., June 15, 2004; 64(12): 4209 - 4217.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
R. K. H. Lo and Y. H. Wong
Signal Transducer and Activator of Transcription 3 Activation by the {delta}-Opioid Receptor via G{alpha}14 Involves Multiple Intermediates
Mol. Pharmacol., June 1, 2004; 65(6): 1427 - 1439.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2003