Beschreibung:
<jats:p>While the epidermal growth factor receptor (<jats:styled-content style="fixed-case">EGFR</jats:styled-content>) is an established regulator of skin development and homeostasis, the functions of the related tyrosine kinase receptors <jats:styled-content style="fixed-case">ERBB</jats:styled-content>2 and <jats:styled-content style="fixed-case">ERBB</jats:styled-content>3 in this tissue have only recently been examined. Previously reported, skin‐specific deletion of each of these receptors in mice resulted in similar defects in keratinocyte proliferation and migration, resulting in impaired wound healing and tumorigenesis. Because both <jats:styled-content style="fixed-case">ERBB</jats:styled-content>2 and <jats:styled-content style="fixed-case">ERBB</jats:styled-content>3 are targets for treating an array of cancer types, it is important to examine the consequences of receptor inhibition in human keratinocytes. Here, we employed the <jats:styled-content style="fixed-case">CRISPR</jats:styled-content>/Cas9 technology to generate HaCaT cells (an established human keratinocyte cell line) lacking <jats:styled-content style="fixed-case">ERBB</jats:styled-content>2 or <jats:styled-content style="fixed-case">ERBB</jats:styled-content>3. HaCaT clones lacking <jats:styled-content style="fixed-case">ERBB</jats:styled-content>2 or <jats:styled-content style="fixed-case">ERBB</jats:styled-content>3 showed comparable reductions in cell proliferation as assessed by BrdU staining. Apoptosis, in contrast, was reduced in <jats:styled-content style="fixed-case">ERBB</jats:styled-content>3‐deficient HaCaT cells only. Assessment of cell migration using a wound healing (scratch) assay showed that the closure of the wound gaps was completed by 48 h in mock and in <jats:styled-content style="fixed-case">ERBB</jats:styled-content>3 knockout clones. In contrast, this process was considerably delayed in <jats:styled-content style="fixed-case">ERBB</jats:styled-content>2 knockout clones, and a complete closure of the gap in the latter cells did not occur before 72 h. In conclusion, both <jats:styled-content style="fixed-case">ERBB</jats:styled-content>2 and <jats:styled-content style="fixed-case">ERBB</jats:styled-content>3 are essential for normal proliferation of skin keratinocytes, but in contrast to <jats:styled-content style="fixed-case">ERBB</jats:styled-content>3, <jats:styled-content style="fixed-case">ERBB</jats:styled-content>2 is essential for migration of human keratinocytes. These observations might bear significance to patient adverse effects of therapeutic agents targeting <jats:styled-content style="fixed-case">ERBB</jats:styled-content>2 and <jats:styled-content style="fixed-case">ERBB</jats:styled-content>3.</jats:p>