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Phenotype switching in melanoma cells: MITF regulates the expression of CDH1 through E-boxes in an intronic region
Journal article   Open access   Peer reviewed

Phenotype switching in melanoma cells: MITF regulates the expression of CDH1 through E-boxes in an intronic region

Evangeline Breeta Raja David Isac, Sara Sigurbjörnsdóttir, Ramile Dilshat, Robert A Cornell, Colin Kenny and Eiríkur Steingrímsson
Journal of investigative dermatology, Vol.146(6`), pp.1635-1648.E4
06/2026
DOI: 10.1016/j.jid.2025.11.008
PMID: 41314510
url
https://doi.org/10.1016/j.jid.2025.11.008View
Published (Version of record) Open Access

Abstract

Melanoma cells evade drug treatment by changing their phenotype from proliferative to migrative cells and vice versa in a process known as phenotype switching. The Microphthalmia-associated transcription factor (MITF) is a key regulator of phenotype switching in melanoma. Previous studies have shown that loss of MITF affects the expression of epithelial-to-mesenchymal transition (EMT) marker genes such as E-Cadherin (CDH1) and N-Cadherin (CDH2). However, the specific roles of CDH1 and CDH2 in phenotype switching, as well as their direct correlation with MITF, remains unclear. This study aimed to investigate how MITF regulates CDH1 expression in melanoma. The results showed that a 1 kb intronic CDH1 fragment (CDH1-B) leads to MITF-dependent activation of CDH1 expression through specific binding sites. Although MITF represses the expression of the EMT transcription factors SNAIL, ZEB1 and TWIST1, knockdown of SNAI1 and TWIST1 did not affect CDH1 expression or expression from the CDH1-B element. Also, ZEB1 did not affect expression from the CDH1-B element, suggesting that MITF activates CDH1 directly through this regulatory element. Our results show the direct role of MITF in regulating CDH1 expression in melanoma, highlighting an important step in the phenotype switching process.
 Transcription Phenotype Switching MITF CDH1 Melanoma

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