Issues

Internalization of activated epidermal growth factor receptor (EGFR) via early endosomes plays a key role in mediating EGFR signaling and activity. The cover depicts a three-dimensional rendering of EGFR-containing endosomes as calculated from the average immunofluorescence intensity of EGFR-phospho 1068. The authors found that non-cancerous MCF10A cells exhibited a rapid increase in endosome size and phospho-1068 EGFR, which returned quickly to baseline levels. By contrast, cancerous MDA-MB-231 cells exhibited a slightly delayed increase in these metrics and larger endosomes overall, which persisted over a longer duration and correlated with sustained EGFR signaling. Concordantly, modulation of endosome size via ablation or overexpression of Rab4A was shown to harbor implications for the strength and duration of EGFR activation in breast cancer cells. For more information, see the Highlight on page 669 and the article on page 757.