|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 279, Issue 6, 5017-5024, February 6, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A Dominant Negative Type I Insulin-like Growth Factor Receptor Inhibits Metastasis of Human Cancer Cells*
From the
Department of Medicine and Cancer Center, University of Minnesota, Minnesota 55455 and Breast Center, Baylor College of Medicine, Houston, Texas 77030
We have previously shown that LCC6 wild-type (WT) cells, a metastatic variant of MDA-MB-435 cancer cells originally derived from a breast cancer patient, exhibit enhanced motility in response to IGF-I compared with the parent MDA-MB-435 cells. To further understand the role of the type I insulin-like growth factor (IGF) receptor (IGF1R) in cancer metastasis we inhibited signaling via IGF1R using a C-terminal-truncated IGF1R. The truncated receptor retains the ligand binding domain but lacks the autophosphorylated tyrosine residues in the carboxyl terminus. Cells stably transfected with this truncated receptor (LCC6-DN cells) overexpressed the truncated IGF1R messenger RNA nearly 50-fold over endogenous receptor. The truncated receptor in the LCC6-DN cells behaved in a dominant negative manner to inhibit endogenous IGF1R activation by IGF-I. Compared with the LCC6-WT cells, LCC6-DN cells failed to phosphorylate the adaptor proteins insulin receptor substrate-1 and -2 in response to IGF-I and did not activate Akt after exposure to IGF-I. Unlike LCC6-WT cells, LCC6-DN cells did not show enhanced motility in response to IGF-I. To assay for metastasis, LCC6-WT and LCC6-DN cells were injected into the mammary fat pads of mice, and the primary xenograft tumors were removed after 21 days. Mice sacrificed 5 weeks later showed multiple lung metastases derived from LCC-WT xenografts, whereas mice harboring LCC6-DN xenografts showed no lung metastases. Our data show that IGF1R can regulate several aspects of the malignant phenotype. In these cells, metastasis but not proliferation requires IGF1R function.
Received for publication, May 22, 2003 , and in revised form, November 10, 2003.
* This work was supported by U. S. Army Medical Research and Material Command Grant DAMD17-00-1-0347 (to D. S.), National Institutes of Health Grant R01 CA74285, and Public Health Service Cancer Center Support Grant P30 CA77398. The costs of publication of this article were defrayed in part by the payment of page charges. This 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: University of Minnesota Cancer Center, MMC 806, 420 Delaware St. SE, Minneapolis, MN 55455. Tel.: 612-626-8487; Fax: 612-626-4842; E-mail: yeexx006{at}umn.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  X. Zeng, D. Sachdev, H. Zhang, M. Gaillard-Kelly, and D. Yee Sequencing of Type I Insulin-Like Growth Factor Receptor Inhibition Affects Chemotherapy Response In vitro and In vivo Clin. Cancer Res., April 15, 2009; 15(8): 2840 - 2849. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Kleinberg, T. L. Wood, P. A. Furth, and A. V. Lee Growth Hormone and Insulin-Like Growth Factor-I in the Transition from Normal Mammary Development to Preneoplastic Mammary Lesions Endocr. Rev., February 1, 2009; 30(1): 51 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Pankratz, E. Y. Tan, Y. Fine, A. M. Mercurio, and L. M. Shaw Insulin Receptor Substrate-2 Regulates Aerobic Glycolysis in Mouse Mammary Tumor Cells via Glucose Transporter 1 J. Biol. Chem., January 23, 2009; 284(4): 2031 - 2037. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Litzenburger, H.-J. Kim, I. Kuiatse, J. M. Carboni, R. M. Attar, M. M. Gottardis, C. R. Fairchild, and A. V. Lee BMS-536924 Reverses IGF-IR-Induced Transformation of Mammary Epithelial Cells and Causes Growth Inhibition and Polarization of MCF7 Cells Clin. Cancer Res., January 1, 2009; 15(1): 226 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. K. Saxena, L. Taliaferro-Smith, B. B. Knight, D. Merlin, F. A. Anania, R. M. O'Regan, and D. Sharma Bidirectional Crosstalk between Leptin and Insulin-like Growth Factor-I Signaling Promotes Invasion and Migration of Breast Cancer Cells via Transactivation of Epidermal Growth Factor Receptor Cancer Res., December 1, 2008; 68(23): 9712 - 9722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Matthews, M. J. Taggart, and M. Westwood Modulation of Caveolin-1 Expression Can Affect Signalling through the Phosphatidylinositol 3-Kinase/Akt Pathway and Cellular Proliferation in Response to Insulin-Like Growth Factor I Endocrinology, October 1, 2008; 149(10): 5199 - 5208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. H. Ibrahim, S. A. Byron, X. Cui, A. V. Lee, and D. Yee Progesterone Receptor-B Regulation of Insulin-Like Growth Factor-Stimulated Cell Migration in Breast Cancer Cells via Insulin Receptor Substrate-2 Mol. Cancer Res., September 1, 2008; 6(9): 1491 - 1498. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Sachdev and D. Yee Disrupting Insulin-Like Growth Factor Signaling as a Potential Cancer Therapy Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 39 - 58. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. G. Hollier, J. A. Kricker, D. R. Van Lonkhuyzen, D. I. Leavesley, and Z. Upton Substrate-Bound Insulin-Like Growth Factor (IGF)-I-IGF Binding Protein-Vitronectin-Stimulated Breast Cell Migration Is Enhanced by Coactivation of the Phosphatidylinositide 3-Kinase/AKT Pathway by {alpha}v-Integrins and the IGF-I Receptor Endocrinology, March 1, 2008; 149(3): 1075 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Barnes, K. Ohshiro, S. K. Rayala, A. K. El-Naggar, and R. Kumar Insulin-like Growth Factor Receptor as a Therapeutic Target in Head and Neck Cancer Clin. Cancer Res., July 15, 2007; 13(14): 4291 - 4299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. de Bono, G. Attard, A. Adjei, M. N. Pollak, P. C. Fong, P. Haluska, L. Roberts, C. Melvin, M. Repollet, D. Chianese, et al. Potential Applications for Circulating Tumor Cells Expressing the Insulin-Like Growth Factor-I Receptor Clin. Cancer Res., June 15, 2007; 13(12): 3611 - 3616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Conti, G. Regis, A. Longo, P. Bernabei, R. Chiarle, M. Giovarelli, and F. Novelli In the absence of IGF-1 signaling, IFN-{gamma} suppresses human malignant T-cell growth Blood, March 15, 2007; 109(6): 2496 - 2504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Manara, L. Landuzzi, P. Nanni, G. Nicoletti, D. Zambelli, P. L. Lollini, C. Nanni, F. Hofmann, C. Garcia-Echeverria, P. Picci, et al. Preclinical In vivo Study of New Insulin-Like Growth Factor-I Receptor-Specific Inhibitor in Ewing's Sarcoma Clin. Cancer Res., February 15, 2007; 13(4): 1322 - 1330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang, A. M. Pelzer, D. T. Kiang, and D. Yee Down-regulation of Type I Insulin-like Growth Factor Receptor Increases Sensitivity of Breast Cancer Cells to Insulin Cancer Res., January 1, 2007; 67(1): 391 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Sachdev and D. Yee Disrupting insulin-like growth factor signaling as a potential cancer therapy Mol. Cancer Ther., January 1, 2007; 6(1): 1 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Whitson, B. A. Jacobson, S. Frizelle, M. R. Patel, D. Yee, M. A. Maddaus, and R. A. Kratzke Effects of insulin-like growth factor-1 receptor inhibition in mesothelioma. Ann. Thorac. Surg., September 1, 2006; 82(3): 996 - 1001. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A M Lorincz and S Sukumar Molecular links between obesity and breast cancer. Endocr. Relat. Cancer, June 1, 2006; 13(2): 279 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Menu, H. Jernberg-Wiklund, T. Stromberg, H. De Raeve, L. Girnita, O. Larsson, M. Axelson, K. Asosingh, K. Nilsson, B. Van Camp, et al. Inhibiting the IGF-1 receptor tyrosine kinase with the cyclolignan PPP: an in vitro and in vivo study in the 5T33MM mouse model Blood, January 15, 2006; 107(2): 655 - 660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Feng, Z. Zhu, X. Xiao, V. Choudhry, J. C. Barrett, and D. S. Dimitrov Novel human monoclonal antibodies to insulin-like growth factor (IGF)-II that potently inhibit the IGF receptor type I signal transduction function Mol. Cancer Ther., January 1, 2006; 5(1): 114 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Miller and D. Yee Type I Insulin-like Growth Factor Receptor as a Therapeutic Target in Cancer Cancer Res., November 15, 2005; 65(22): 10123 - 10127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. C. Lewis, D. S. Klimstra, N. D. Socci, S. Xu, J. A. Koutcher, and H. E. Varmus The Absence of p53 Promotes Metastasis in a Novel Somatic Mouse Model for Hepatocellular Carcinoma Mol. Cell. Biol., February 15, 2005; 25(4): 1228 - 1237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. H. Ibrahim and D. Yee Insulin-Like Growth Factor-I and Breast Cancer Therapy Clin. Cancer Res., January 15, 2005; 11(2): 944s - 950s. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Lynch, P. I. Vodyanik, D. Boettiger, and M. A. Guvakova Insulin-like Growth Factor I Controls Adhesion Strength Mediated by {alpha}5{beta}1 Integrins in Motile Carcinoma Cells Mol. Biol. Cell, January 1, 2005; 16(1): 51 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Pold, K. Krysan, A. Pold, M. Dohadwala, N. Heuze-Vourc'h, J. T. Mao, K. L. Riedl, S. Sharma, and S. M. Dubinett Cyclooxygenase-2 Modulates the Insulin-Like Growth Factor Axis in Non-Small-Cell Lung Cancer Cancer Res., September 15, 2004; 64(18): 6549 - 6555. [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 |