Overexpression of EGFR and c‐erbB2 causes enhanced cell migration in human breast cancer cells and NIH3T3 fibroblasts

Verbeek, Bianca S.; Adriaansen-Slot, Sabrina S.; Vroom, Thea M.; Beckers, Thomas; Rijksen, Gert

doi:10.1016/s0014-5793(98)00224-5

Cited by 133 publications

(82 citation statements)

References 30 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…EGFR overexpression in breast cancer cells induces migration, suggesting an important role for EGFR in cell motility. 39 budding. Cargo internalization into ILVs requires the actions of ESCRT proteins and serves to effectively terminate receptor signaling.…”

Section: Discussionmentioning

confidence: 99%

Bif-1 suppresses breast cancer cell migration by promoting EGFR endocytic degradation

Runkle

Meyerkord

Desai

et al. 2012

Cancer Biology & Therapy

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Bif-1 suppresses breast cancer cell migration by promoting EGFR endocytic degradation

Runkle

Meyerkord

Desai

et al. 2012

Cancer Biology & Therapy

View full text Add to dashboard Cite

“…Since it is the development of metastatic disease that is primarily responsible for cancer mortality, understanding the mechanisms that facilitate metastatic tumor progression is of great importance. A wide number of molecules such as cytokines, chemokines and growth factors have been implicated to be responsible for the metastatic property of breast cancer cells (Youngs et al, 1997;Verbeek et al, 1998;Kim and Muller, 1999;Hilakivi-Clarke, 2000;Hyder et al, 2001;McEarchern et al, 2001;Muller et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Regulation of CXCR4-mediated chemotaxis and chemoinvasion of breast cancer cells

et al. 2004

View full text Add to dashboard Cite

The chemokine-CXCL12 and its receptor, CXCR4, have recently been shown to play an important role in regulating the directional migration of breast cancer cells to sites of metastasis. In the present study, we showed that CXCL12 enhanced the chemotaxis, chemoinvasion and adhesive properties of breast cancer cells; parameters that are critical for development of metastasis. We have also evaluated the signaling mechanisms that regulate CXCL12-induced and CXCR4-mediated breast cancer cell motility and invasion. These studies revealed that CXCL12 induces the tyrosine phosphorylation of focal adhesion kinase (FAK) at residues 397 and 577, and of RAFTK/Pyk2 at residues 402 and 579/580. The cytoskeletal proteins paxillin and Crk, as well as tyrosine phosphatase SHP2 and adaptor protein Cbl, were also phosphorylated. CXCL12 induced the activation of PI 3-kinase, and increased its association with Cbl and SHP2. PI 3-kinase, RAFTK/Pyk2 and tyrosine phosphatase inhibitors significantly blocked CXCL12-induced chemotaxis and chemoinvasion. The role of SHP2 and Cbl in CXCL12-induced chemotaxis and chemoinvasion in breast cancer cells was further defined by transiently overexpressing wild-type SHP2, wild-type Cbl, dominantnegative SHP2, Cbl mutants 70Z/3 and G306E or double transfectants of the Cbl and SHP2 constructs. We found a novel role of Cbl in CXCL12-induced chemotaxis, which may be mediated through the activation and formation of a multimeric complex comprised of Cbl, SHP2 and PI 3-kinase. We also observed the activation of matrix metalloproteinases 2 and 9 upon CXCL12 stimulation. These studies provide new information regarding signaling pathways that may regulate CXCL12-induced metastasis in breast cancer cells.

show abstract

“…Alternatively, decorin itself could be directly involved in a mechanism regulating the behavior of metastatic cells by lowering their tendency to spread. Overexpression of EGFR and ErbB2 has been shown to stimulate cell migration, which is an important step in metastasis (Verbeek et al, 1998). Breaking the signaling cascade of the EGFR pathway should, therefore, correlate with reduced metastatic spread and better overall prognosis in vivo.…”

mentioning

confidence: 99%

Decorin prevents metastatic spreading of breast cancer

et al. 2004

View full text Add to dashboard Cite

Metastases in breast cancer are a vital concern in treatment, with epidermal growth factor receptor and ErbB2 strongly implicated in mediating tumor invasion and spreading. In this study, we investigated the role of decorin in suppressing both primary breast carcinomas and pulmonary metastases. We show that decorin causes marked growth suppression both in vitro and in vivo using a metastatic breast cancer cell line and an orthotopic mammary carcinoma model. Treatment with decorin protein core reduced primary tumor growth by 70% and eliminated observed metastases. An adenoviral vector containing the decorin transgene caused primary tumor retardation of 70%, in addition to greatly reducing observed metastases. Moreover, we demonstrate that ErbB2 phosphorylation and total receptor protein levels are reduced in this model system upon de novo expression of decorin under the control of a doxycycline-inducible promoter. Primary tumor growth in vivo was reduced by up to 67% upon decorin induction, and pulmonary metastases were markedly hampered as well. These effects are likely occurring through decorin's long-term downregulation of the ErbB2 tyrosine kinase cascade. These results demonstrate a novel role for decorin in reduction or prevention of tumor metastases in this breast cancer model and could eventually lead to improved therapeutics for metastatic breast cancer.

show abstract

Overexpression of EGFR and c‐erbB2 causes enhanced cell migration in human breast cancer cells and NIH3T3 fibroblasts

Cited by 133 publications

References 30 publications

Bif-1 suppresses breast cancer cell migration by promoting EGFR endocytic degradation

Bif-1 suppresses breast cancer cell migration by promoting EGFR endocytic degradation

Regulation of CXCR4-mediated chemotaxis and chemoinvasion of breast cancer cells

Decorin prevents metastatic spreading of breast cancer

Contact Info

Product

Resources

About