The involvement of lipid rafts in epidermal growth factor-induced chemotaxis of breast cancer cells.
Metastasis is the major cause of morbidity and mortality in cancer. Recent studies reveal a role of chemotaxis in cancer cell metastasis. Epidermal growth factor receptors (EGFR) have potent chemotactic effects on human breast cancer cells. Lipid rafts, organized microdomain on plasma membranes, regulate the activation of many membrane receptors. In the current study, we investigated the role of lipid rafts in EGFR-mediated cancer cell chemotaxis. Our confocal microscopy results suggested that EGFR co-localized with GM1-positive rafts. Disrupting rafts with methyl-beta-cyclodextrin (mbetaCD) inhibited EGF-induced chemotaxis of human breast cancer cells. Supplementation with cholesterol reversed the inhibitory effects. Pretreatment with mbetaCD also impaired directional migration of cells in an in vitro "wound healing" assay, EGF-induced cell adhesion, actin polymerization, Akt phosphorylation and protein kinase Czeta (PKCzeta) translocation. Taken together, our study indicated that integrity of lipid rafts was critical in EGF-induced chemotaxis of human breast cancer cells.
Liu
Ying
Y
Beijing National Laboratory for Molecular Sciences (BNLMS) and Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
Sun
Ronghua
R
Wan
Wuzhou
W
Wang
Jingna
J
Oppenheim
Joost J
JJ
Chen
Lin
L
Zhang
Ning
N
D001943:Breast Neoplasms / Q000473:pathology*; D002277:Carcinoma / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects*; D002784:Cholesterol / Q000032:analysis; D004705:Endocytosis / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D004815:Epidermal Growth Factor; D002784:Cholesterol; C512478:EGFR protein, human; D066246:ErbB Receptors