Abstract
Activation of EGFR signaling induces collective migration of keratinocytes during wound healing and tumor invasion. However, collective behaviors of keratinocytes by EGFR activation with different growth capacity have not been elucidated. Here, we show coupling of proliferative and EGF-induced migratory capacities of cultured human epidermal keratinocytes. EGF immediately induced collective migration and contraction of keratinocytes with significant and limited proliferative capacities, respectively. These collective behaviors were caused through the phosphorylation of myosin regulatory light chain and subsequent actomyosin interaction. PI3K/Rac1 activity directed the actin filament organization and modes of EGF response in keratinocytes. Furthermore, Rac1 activity was also essential for reproductive capacity of keratinocytes. This study links proliferative and EGF-induced migratory capacities of keratinocytes through PI3K/Rac1 signaling and suggests that collective migration of keratinocytes activated by EGFR signaling with higher reproductive and tumor-initiating capacities contributes considerably to re-epithelialization, and tumor invasion and metastasis.
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