| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Institut für Klinische Chemie und Laboratoriumsmedizin, 48149 Münster, Germany; and
Institut für Immunologie, Universität Witten/Herdecke, Witten 58453, Germany
1Correspondence: Institut für Klinische Chemie und Laboratoriumsmedizin, Albert-Schweitzer-Str. 33, 48149 Münster, Germany. E-mail: brandt{at}uni-muenster.de
Separate mechanisms for oncogenesis and metastasis have been postulated. We show here that prolonged and invasive cell migration, a key mechanism in cancer metastasis, is linked to c-erbB-2 signaling. Cell lines with c-erbB-2 and EGFR expression and transphosphorylation activity display a high transendothelial invasiveness in an endothelial-extracellular matrix model mimicking a capillary vessel wall in vitro. Tyrosine-phosphorylated c-erbB-2 receptors and EGFR are localized predominantly in areas of the cell with high membrane extension activity. On the molecular level, there is a subtle cross talk between the transmembrane signaling molecule c-erbB-2 and the actin cytoskeleton at multiple levels, including the generation of the second messenger PIP2 and the mobilization of the actin-regulatory protein gelsolin. Our data strongly suggest that c-erbB-2, especially in a heterodimer with EGFR, is closely involved in signaling pathways, inducing alterations in cell morphology that are required for a human breast cancer cell to become motile and conceivably metastatic.—Brandt, B. H., Roetger, A., Dittmar, T., Nikolai, G., Seeling, M., Merschjann, A., Nofer, J.-R., Dehmer-Möller, G., Junker, R., Assmann, G., Zaenker. K. S. c-erbB-2/EGFR as dominant heterodimerization partners determine a motogenic phenotype in human breast cancer cells.
Key Words: F-actin • gelsolin • epidermal growth factor • HUVEC
This article has been cited by other articles:
|
|
 |
|
  B. H Brandt Single/Oligo-Cell PCR: Needs, Perspectives, and Limitations Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 625 - 628. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Seidman, D. Berry, C. Cirrincione, L. Harris, H. Muss, P. K. Marcom, G. Gipson, H. Burstein, D. Lake, C. L. Shapiro, et al. Randomized Phase III Trial of Weekly Compared With Every-3-Weeks Paclitaxel for Metastatic Breast Cancer, With Trastuzumab for all HER-2 Overexpressors and Random Assignment to Trastuzumab or Not in HER-2 Nonoverexpressors: Final Results of Cancer and Leukemia Group B Protocol 9840 J. Clin. Oncol., April 1, 2008; 26(10): 1642 - 1649. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Song, C. Zhao, L. Dong, M. Fu, L. Xue, Z. Huang, T. Tong, Z. Zhou, A. Chen, Z. Yang, et al. Overexpression of cyclin B1 in human esophageal squamous cell carcinoma cells induces tumor cell invasive growth and metastasis Carcinogenesis, February 1, 2008; 29(2): 307 - 315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Luangdilok, C. Box, L. Patterson, W. Court, K. Harrington, L. Pitkin, P. Rhys-Evans, P. O-charoenrat, and S. Eccles Syk Tyrosine Kinase Is Linked to Cell Motility and Progression in Squamous Cell Carcinomas of the Head and Neck Cancer Res., August 15, 2007; 67(16): 7907 - 7916. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Kersting, C. Gebert, K. Agelopoulos, H. Schmidt, P. J. van Diest, H. Juergens, W. Winkelmann, M. Kevric, G. Gosheger, B. Brandt, et al. Epidermal Growth Factor Receptor Expression in High-Grade Osteosarcomas Is Associated with a Good Clinical Outcome Clin. Cancer Res., May 15, 2007; 13(10): 2998 - 3005. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Kumar, M. H. Zaman, H.-D. Kim, and D. A. Lauffenburger A High-Throughput Migration Assay Reveals HER2-Mediated Cell Migration Arising from Increased Directional Persistence Biophys. J., August 15, 2006; 91(4): L32 - L34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B Brandt, D Kemming, J Packeisen, R Simon, M Helms, U Feldmann, A Matuschek, C Kersting, B Hinrichs, J-M Bidart, et al. Expression of early placenta insulin-like growth factor in breast cancer cells provides an autocrine loop that predominantly enhances invasiveness and motility Endocr. Relat. Cancer, December 1, 2005; 12(4): 823 - 837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Haslekas, K. Breen, K. W. Pedersen, L. E. Johannessen, E. Stang, and I. H. Madshus The Inhibitory Effect of ErbB2 on Epidermal Growth Factor-induced Formation of Clathrin-coated Pits Correlates with Retention of Epidermal Growth Factor Receptor-ErbB2 Oligomeric Complexes at the Plasma Membrane Mol. Biol. Cell, December 1, 2005; 16(12): 5832 - 5842. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Qi, N. Chen, J. Wang, and C.-H. Siu Transendothelial Migration of Melanoma Cells Involves N-Cadherin-mediated Adhesion and Activation of the {beta}-Catenin Signaling Pathway Mol. Biol. Cell, September 1, 2005; 16(9): 4386 - 4397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Orr, D. Hu, S. Ozcelik, L. K. Opresko, H. S. Wiley, and S. D. Colson Cholesterol Dictates the Freedom of EGF Receptors and HER2 in the Plane of the Membrane Biophys. J., August 1, 2005; 89(2): 1362 - 1373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Muller-Tidow, S. Diederichs, E. Bulk, T. Pohle, B. Steffen, J. Schwable, S. Plewka, M. Thomas, R. Metzger, P. M. Schneider, et al. Identification of Metastasis-Associated Receptor Tyrosine Kinases in Non-Small Cell Lung Cancer Cancer Res., March 1, 2005; 65(5): 1778 - 1782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Khoury, M. A. Naujokas, D. Zuo, V. Sangwan, M. M. Frigault, S. Petkiewicz, D. L. Dankort, W. J. Muller, and M. Park HGF Converts ErbB2/Neu Epithelial Morphogenesis to Cell Invasion Mol. Biol. Cell, February 1, 2005; 16(2): 550 - 561. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Gerber, N. Sal-Man, and Y. Shai Two Motifs within a Transmembrane Domain, One for Homodimerization and the Other for Heterodimerization J. Biol. Chem., May 14, 2004; 279(20): 21177 - 21182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Hommelgaard, M. Lerdrup, and B. van Deurs Association with Membrane Protrusions Makes ErbB2 an Internalization-resistant Receptor Mol. Biol. Cell, April 1, 2004; 15(4): 1557 - 1567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Onn, A. M. Correa, M. Gilcrease, T. Isobe, E. Massarelli, C. D. Bucana, M. S. O'Reilly, W. K. Hong, I. J. Fidler, J. B. Putnam, et al. Synchronous Overexpression of Epidermal Growth Factor Receptor and HER2-neu Protein Is a Predictor of Poor Outcome in Patients with Stage I Non-Small Cell Lung Cancer Clin. Cancer Res., January 1, 2004; 10(1): 136 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Hendriks, H. S. Wiley, and D. Lauffenburger HER2-Mediated Effects on EGFR Endosomal Sorting: Analysis of Biophysical Mechanisms Biophys. J., October 1, 2003; 85(4): 2732 - 2745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Atalay, F. Cardoso, A. Awada, and M. J. Piccart Novel therapeutic strategies targeting the epidermal growth factor receptor (EGFR) family and its downstream effectors in breast cancer Ann. Onc., September 1, 2003; 14(9): 1346 - 1363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Hendriks, L. K. Opresko, H. S. Wiley, and D. Lauffenburger Quantitative Analysis of HER2-mediated Effects on HER2 and Epidermal Growth Factor Receptor Endocytosis: DISTRIBUTION OF HOMO- AND HETERODIMERS DEPENDS ON RELATIVE HER2 LEVELS J. Biol. Chem., June 20, 2003; 278(26): 23343 - 23351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Hendriks, L. K. Opresko, H. S. Wiley, and D. Lauffenburger Coregulation of Epidermal Growth Factor Receptor/Human Epidermal Growth Factor Receptor 2 (HER2) Levels and Locations: Quantitative Analysis of HER2 Overexpression Effects Cancer Res., March 1, 2003; 63(5): 1130 - 1137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Thor, S. M. Edgerton, S. Liu, D. H. Moore II, and D. J. Kwiatkowski Gelsolin as a Negative Prognostic Factor and Effector of Motility in erbB-2-positive Epidermal Growth Factor Receptor-positive Breast Cancers Clin. Cancer Res., August 1, 2001; 7(8): 2415 - 2424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Font de Mora and M. Brown AIB1 Is a Conduit for Kinase-Mediated Growth Factor Signaling to the Estrogen Receptor Mol. Cell. Biol., July 15, 2000; 20(14): 5041 - 5047. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
