Cell-Matrix Interactions in Breast Carcinoma Invasion
Final rept. 15 Dec 1994-14 Dec 1999
NEW YORK UNIV MEDICAL CENTER NY
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Recent evidence suggests that EGF may influence human breast cancer progression via migratory pathways that, at least in part, appear to be dissociated from the proliferative pathways. We have shown previously that activation of the EGF receptor EGFR leads to tyrosine phosphorylation of the Beta4 subunit of Alpha6 Beta4 integrin, followed by disruption of hemidesmosomes and promotion of cell migration. The results reported here indicate that a fraction of EGFR is constitutively associated with a6Beta4. We also found that the tyrosine kinase Fyn mediates EGFR induced phosphorylation of the Beta4 cytoplasmic tail and disruption of the hemidesmosomes. Inhibition of Fyn activity leads to stabilization of hemidesmosomes and suppresses migration and invasion by breast carcinoma cells. These findings suggest that EGFR-mediated disruption of hemidesmosomes is a prerequisite for normal cell migration and tumor invasion.
- Medicine and Medical Research