|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 278, Issue 5, 3275-3285, January 31, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Departments of Transforming growth factor-
Autocrine Transforming Growth Factor-
Signaling
Mediates Smad-independent Motility in Human Cancer Cells*
,§¶
Cancer Biology and
§ Medicine and ¶ Vanderbilt-Ingram Cancer Center,
Vanderbilt University School of Medicine, Nashville, Tennessee
37232
(TGF-)
is a pleiotropic growth factor that plays a critical role in modulating
cell growth, differentiation, and plasticity. There is increasing
evidence that after cells lose their sensitivity to TGF--mediated
growth inhibition, autocrine TGF- signaling may potentially promote tumor cell motility and invasiveness. To understand the molecular mechanisms by which autocrine TGF- may selectively contribute to
tumor cell motility, we have generated MDA-MB-231 breast cancer cells
stably expressing a kinase-inactive type II TGF- receptor (TRII-K277R). Our data indicate that TRII-K277R is expressed, can
associate with the type I TGF- receptor, and block both
Smad-dependent and -independent signaling pathways
activated by TGF-. In addition, wound closure and transwell
migration assays indicated that the basal migratory potential of
TRII-K277R expressing cells was impaired. The impaired motility of
TRII-K277R cells could be restored by reconstituting TGF-
signaling with a constitutively active TGF- type I receptor
(ALK5TD) but not by reconstituting Smad signaling
with Smad2/4 or Smad3/4 expression. In addition, the levels of
ALK5TD expression sufficient to restore motility in the
cells expressing TRII-K277R were associated with an increase in
phosphorylation of Akt and extracellular signal-regulated kinase 1/2
but not Smad2. These data indicate that different signaling pathways
require different thresholds of TGF- activation and suggest that
TGF- promotes motility through mechanisms independent of Smad
signaling, possibly involving activation of the phosphatidylinositol
3-kinase/Akt and/or mitogen-activated protein kinase pathways.
*
Fluorescence microscopy images were acquired through the use
of the Vanderbilt University Medical Center Cell Imaging Core Resource
supported by National Institutes of Health Grants CA68485 and DK20593.
This work was supported in part by United States Army Medical Research
and Materiel Command Awards DAMD17-98-1-8263 (to N. D.), BC011342 (to
A. V. B.), and DAMD17-98-1-8262 (to C. L. A.), by Public
Health Service Grants CA62212 (to C. L. A.) and CA95263 (to
A. V. B.), and by Vanderbilt-Ingram Cancer Center Support Grant
CA68485.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Division of
Oncology, Vanderbilt University School of Medicine, 2220 Pierce Ave., 777 Preston Research Bldg., Nashville, TN 37232-6307. Tel.:
615-936-3524; Fax: 615-936-1790; E-mail:
carlos.arteaga@vanderbilt.edu.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Geismann, M. Morscheck, D. Koch, F. Bergmann, H. Ungefroren, A. Arlt, M.-S. Tsao, M. G. Bachem, P. Altevogt, B. Sipos, et al. Up-regulation of L1CAM in Pancreatic Duct Cells Is Transforming Growth Factor {beta}1- and Slug-Dependent: Role in Malignant Transformation of Pancreatic Cancer Cancer Res., May 15, 2009; 69(10): 4517 - 4526. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Zhang, B. T. Helfand, T. L. Jang, L. J. Zhu, L. Chen, X. J. Yang, J. Kozlowski, N. Smith, S. D. Kundu, G. Yang, et al. Nuclear Factor-{kappa}B-Mediated Transforming Growth Factor-{beta}-Induced Expression of Vimentin Is an Independent Predictor of Biochemical Recurrence after Radical Prostatectomy Clin. Cancer Res., May 15, 2009; 15(10): 3557 - 3567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Criswell, N. Dumont, J. V. Barnett, and C. L. Arteaga Knockdown of the Transforming Growth Factor-{beta} Type III Receptor Impairs Motility and Invasion of Metastatic Cancer Cells Cancer Res., September 15, 2008; 68(18): 7304 - 7312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Wang, B. Xiang, M. Guix, M. G. Olivares, J. Parker, C. H. Chung, A. Pandiella, and C. L. Arteaga Transforming Growth Factor {beta} Engages TACE and ErbB3 To Activate Phosphatidylinositol-3 Kinase/Akt in ErbB2-Overexpressing Breast Cancer and Desensitizes Cells to Trastuzumab Mol. Cell. Biol., September 15, 2008; 28(18): 5605 - 5620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. D. Moore, T. Isayeva, G. P. Siegal, and S. Ponnazhagan Silencing of Transforming Growth Factor-{beta}1 In situ by RNA Interference for Breast Cancer: Implications for Proliferation and Migration In vitro and Metastasis In vivo Clin. Cancer Res., August 1, 2008; 14(15): 4961 - 4970. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zhao, K. Venkatasubbarao, J. W. Lazor, J. Sperry, C. Jin, L. Cao, and J. W. Freeman Inhibition of STAT3Tyr705 Phosphorylation by Smad4 Suppresses Transforming Growth Factor {beta}-Mediated Invasion and Metastasis in Pancreatic Cancer Cells Cancer Res., June 1, 2008; 68(11): 4221 - 4228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Rosman, S. Phukan, C.-C. Huang, and B. Pasche TGFBR1*6A Enhances the Migration and Invasion of MCF-7 Breast Cancer Cells through RhoA Activation Cancer Res., March 1, 2008; 68(5): 1319 - 1328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. A. Yoo, M. H. Kang, J. S. Kim, and S. C. Oh Sonic hedgehog signaling promotes motility and invasiveness of gastric cancer cells through TGF-{beta}-mediated activation of the ALK5-Smad 3 pathway Carcinogenesis, March 1, 2008; 29(3): 480 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Criswell and C. L. Arteaga Modulation of NF{kappa}B Activity and E-cadherin by the Type III Transforming Growth Factor beta Receptor Regulates Cell Growth and Motility J. Biol. Chem., November 2, 2007; 282(44): 32491 - 32500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. J. Gaspar, L. Li, A. M. Kapoun, S. Medicherla, M. Reddy, G. Li, G. O'Young, D. Quon, M. Henson, D. L. Damm, et al. Inhibition of Transforming Growth Factor beta Signaling Reduces Pancreatic Adenocarcinoma Growth and Invasiveness Mol. Pharmacol., July 1, 2007; 72(1): 152 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ao, O. E. Franco, D. Park, D. Raman, K. Williams, and S. W. Hayward Cross-talk between Paracrine-Acting Cytokine and Chemokine Pathways Promotes Malignancy in Benign Human Prostatic Epithelium Cancer Res., May 1, 2007; 67(9): 4244 - 4253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Wang, A. Narasanna, C. W. Whitell, F. Y. Wu, D. B. Friedman, and C. L. Arteaga Convergence of p53 and Transforming Growth Factor beta (TGFbeta) Signaling on Activating Expression of the Tumor Suppressor Gene maspin in Mammary Epithelial Cells J. Biol. Chem., February 23, 2007; 282(8): 5661 - 5669. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. B. Friedman, S. E. Wang, C. W. Whitwell, R. M. Caprioli, and C. L. Arteaga Multivariable Difference Gel Electrophoresis and Mass Spectrometry: A Case Study on Transforming Growth Factor-{beta} and ERBB2 Signaling Mol. Cell. Proteomics, January 1, 2007; 6(1): 150 - 169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Barbieri, L. J. Tang, K. A. Brown, and J. A. Pietenpol Loss of p63 Leads to Increased Cell Migration and Up-regulation of Genes Involved in Invasion and Metastasis. Cancer Res., August 1, 2006; 66(15): 7589 - 7597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Y. Wu, S. E. Wang, M. E. Sanders, I. Shin, F. Rojo, J. Baselga, and C. L. Arteaga Reduction of Cytosolic p27Kip1 Inhibits Cancer Cell Motility, Survival, and Tumorigenicity Cancer Res., February 15, 2006; 66(4): 2162 - 2172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Shin, T. Miller, and C. L. Arteaga ErbB Receptor Signaling and Therapeutic Resistance to Aromatase Inhibitors Clin. Cancer Res., February 1, 2006; 12(3): 1008s - 1012s. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dooley, H. M. Said, A. M. Gressner, J. Floege, A. En-Nia, and P. R. Mertens Y-box Protein-1 Is the Crucial Mediator of Antifibrotic Interferon-{gamma} Effects J. Biol. Chem., January 20, 2006; 281(3): 1784 - 1795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tanaka, S. Muto, M. Konno, A. Itai, and H. Matsuda A New I{kappa}B Kinase {beta} Inhibitor Prevents Human Breast Cancer Progression through Negative Regulation of Cell Cycle Transition Cancer Res., January 1, 2006; 66(1): 419 - 426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Moustakas and C.-H. Heldin Non-Smad TGF-{beta} signals J. Cell Sci., August 15, 2005; 118(16): 3573 - 3584. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L O'Rear, L Longobardi, M Torello, B K Law, H L Moses, F Chiarelli, and A Spagnoli Signaling cross-talk between IGF-binding protein-3 and transforming growth factor-{beta} in mesenchymal chondroprogenitor cell growth J. Mol. Endocrinol., June 1, 2005; 34(3): 723 - 737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Wang, F. Y. Wu, I. Shin, S. Qu, and C. L. Arteaga Transforming Growth Factor {beta} (TGF-{beta})-Smad Target Gene Protein Tyrosine Phosphatase Receptor Type Kappa Is Required for TGF-{beta} Function Mol. Cell. Biol., June 1, 2005; 25(11): 4703 - 4715. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Elliott and G. C. Blobe Role of Transforming Growth Factor Beta in Human Cancer J. Clin. Oncol., March 20, 2005; 23(9): 2078 - 2093. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Y. Yi, I. Shin, and C. L. Arteaga Type I Transforming Growth Factor {beta} Receptor Binds to and Activates Phosphatidylinositol 3-Kinase J. Biol. Chem., March 18, 2005; 280(11): 10870 - 10876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wang, Q. Shen, X.-M. Xu, Y.-Q. Chen, and M.-H. Wang Activation of the RON receptor tyrosine kinase attenuates transforming growth factor-{beta}1-induced apoptotic death and promotes phenotypic changes in mouse intestinal epithelial cells Carcinogenesis, January 1, 2005; 26(1): 27 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.S. Prime, M. Pring, M. Davies, and I.C. Paterson TGF-{beta} SIGNAL TRANSDUCTION IN ORO-FACIAL HEALTH AND NON-MALIGNANT DISEASE (PART I) Critical Reviews in Oral Biology & Medicine, November 1, 2004; 15(6): 324 - 336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.S. Prime, M. Davies, M. Pring, and I.C. Paterson THE ROLE OF TGF-{beta} IN EPITHELIAL MALIGNANCY AND ITS RELEVANCE TO THE PATHOGENESIS OF ORAL CANCER (PART II) Critical Reviews in Oral Biology & Medicine, November 1, 2004; 15(6): 337 - 347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Bakin, A. Safina, C. Rinehart, C. Daroqui, H. Darbary, and D. M. Helfman A Critical Role of Tropomyosins in TGF-{beta} Regulation of the Actin Cytoskeleton and Cell Motility in Epithelial Cells Mol. Biol. Cell, October 1, 2004; 15(10): 4682 - 4694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ueda, S. Wang, N. Dumont, J. Y. Yi, Y. Koh, and C. L. Arteaga Overexpression of HER2 (erbB2) in Human Breast Epithelial Cells Unmasks Transforming Growth Factor {beta}-induced Cell Motility J. Biol. Chem., June 4, 2004; 279(23): 24505 - 24513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kobayashi, M. Suzuki, N. Kanayama, and T. Terao Genetic Down-regulation of Phosphoinositide 3-Kinase by Bikunin Correlates with Suppression of Invasion and Metastasis in Human Ovarian Cancer HRA Cells J. Biol. Chem., February 20, 2004; 279(8): 6371 - 6379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. G. Deane, H. Lee, J. Hamaamen, A. Ruley, M. K. Washington, B. LaFleur, S. S. Thorgeirsson, R. Price, and R. D. Beauchamp Enhanced Tumor Formation in Cyclin D1 x Transforming Growth Factor {beta}1 Double Transgenic Mice with Characterization by Magnetic Resonance Imaging Cancer Res., February 15, 2004; 64(4): 1315 - 1322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Saika, Y. Okada, T. Miyamoto, O. Yamanaka, Y. Ohnishi, A. Ooshima, C.-Y. Liu, D. Weng, and W. W.-Y. Kao Role of p38 MAP Kinase in Regulation of Cell Migration and Proliferation in Healing Corneal Epithelium Invest. Ophthalmol. Vis. Sci., January 1, 2004; 45(1): 100 - 109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Muraoka, Y. Koh, L. R. Roebuck, M. E. Sanders, D. Brantley-Sieders, A. E. Gorska, H. L. Moses, and C. L. Arteaga Increased Malignancy of Neu-Induced Mammary Tumors Overexpressing Active Transforming Growth Factor {beta}1 Mol. Cell. Biol., December 1, 2003; 23(23): 8691 - 8703. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |