CXCR4 suppression attenuates EGFRvIII-mediated invasion and induces p38 MAPK-dependent protein trafficking and degradation of EGFRvIII in breast cancer cells

Our previous report has shown that the constitutively activated EGFR variant, EGFRvIII, up-regulates the pro-metastatic chemokine receptor CXCR4 in breast cancer cells. Here we evaluated the biological effect and cell signaling effects of silencing CXCR4 expression in EGFRvIII-expressing breast canc...

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Bibliographic Details
Published inCancer letters Vol. 306; no. 1; pp. 43 - 51
Main Authors Rahimi, Massod, Toth, Theodore A, Tang, Careen K
Format Journal Article
LanguageEnglish
Published Ireland Elsevier Ireland Ltd 01.07.2011
Elsevier Limited
Subjects
Breast cancer
breast neoplasms
Breast Neoplasms - metabolism
Cell adhesion & migration
Cell culture
cell invasion
Cell Line, Tumor
Cell Proliferation
Cell Separation
Chemokines
Cloning
CXCR4
EGFR
EGFRvIII
Female
Flow Cytometry
Gene expression
Gene Expression Regulation, Neoplastic
Gene Silencing
Growth
Hematology, Oncology and Palliative Medicine
Humans
Hypoxia
Invasion
Medical research
Metastasis
Models, Biological
Neoplasm Invasiveness
p38 Mitogen-Activated Protein Kinases - metabolism
Phosphorylation
Proteasome Endopeptidase Complex - metabolism
protein degradation
Protein expression
protein synthesis
Protein Transport
Proteins
Receptor, Epidermal Growth Factor - metabolism
Receptors, CXCR4 - antagonists & inhibitors
small interfering RNA
EGFRvIII
CXCR4
Growth
EGFR
Invasion
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Summary:Our previous report has shown that the constitutively activated EGFR variant, EGFRvIII, up-regulates the pro-metastatic chemokine receptor CXCR4 in breast cancer cells. Here we evaluated the biological effect and cell signaling effects of silencing CXCR4 expression in EGFRvIII-expressing breast cancer cells. Short hairpin RNA (shRNA)-mediated suppression of CXCR4 expression significantly reduced the invasive potential and proliferation of EGFRvIII-expressing breast cancer cells. These cells exhibited a reduction of EGFRvIII activity and protein expression due to increased protein degradation and altered protein trafficking. In conclusion, suppression of CXCR4 inhibits EGFRvIII-mediated breast cancer cell invasion and proliferation.
Bibliography:http://dx.doi.org/10.1016/j.canlet.2011.02.024
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2011.02.024