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Defining markers of different phenotypic states in melanoma is important for understanding disease progression, determining the response to therapy, and defining the molecular mechanisms underpinning phenotype-switching driven by the changing intratumor microenvironment. The ABCB5 transporter is implicated in drug-resistance and has been identified as a marker of melanoma-initiating cells. Indeed ongoing studies are using ABCB5 to define stem cell populations. However, we show here that the ABCB5 is a direct target for the microphthalmia-associated transcription factor MITF and its expression can be induced by β-catenin, a key activator and co-factor for MITF. Consequently, ABCB5 mRNA expression is primarily associated with melanoma cells exhibiting differentiation markers. The results suggest first that ABCB5 is unlikely to represent a marker of de-differentiated melanoma stem cells, and second that ABCB5 may contribute to the non-genetic drug-resistance associated with highly differentiated melanoma cells. To reconcile the apparently conflicting observations in the field, we propose a model in which ABCB5 may mark a slow-cycling differentiated population of melanoma cells.

Original publication

DOI

10.1111/pcmr.12830

Type

Journal article

Journal

Pigment Cell Melanoma Res

Publication Date

01/2020

Volume

33

Pages

112 - 118

Keywords

ABCB5, MITF, melanoma, stem cells, β-catenin, ATP Binding Cassette Transporter, Subfamily B, Base Sequence, Cell Differentiation, Gene Expression Regulation, Neoplastic, Humans, Melanoma, Microphthalmia-Associated Transcription Factor, Phenotype, Skin Neoplasms, beta Catenin