Keratin k15 as a biomarker of epidermal stem cells

Abstract

Keratin 15 (K15) is type I keratin protein co-expressed with the K5/K14 pair present in the basal keratinocytes of all stratified epithelia. Although it is a minor component of the cytoskeleton with a variable expression pattern, nonetheless its expression has been reported as a stem cell marker in the bulge of hair follicles. Conversely, suprabasal expression of K15 has also been reported in both normal and diseased tissues, which is inconsistent with its role as a stem cell marker. Our recently published work has given evidence of the molecular pathways that seem to control the expression of K15 in undifferentiated and differentiated cells. In this article, we have critically reviewed the published work to establish the reliability of K15 as an epidermal stem cell marker.

Figure 1

Schematic representation of the molecular signalling responsible for the differentiation-specific induction of Keratin 15 (K15) expression. Based on our previously published data we propose that K15, although normally a basal-specific keratin, can be induced in differentiating keratinocytes via Protein Kinase-C (PKC)/AP-1 pathway. Differentiation-specific signals, such as loss of cell-surface β1 integrin receptors, increased cell-cell interactions or exposure to tumour-promoter phorbol esters, activate the endogenous PKC signalling, which results in activation of downstream transcription factors AP-1, which in turn induce K15 gene transcription. Blocking the activation of AP-1 by specific inhibitor, SR11302, or by dominant negative form of c-Jun, TAM67, inhibits the transcriptional induction of K15 [61].