Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2023
Höfundar / Authors: Evangeline Breeta Raja David Isac (1), Sara Sigurbjörnsdóttir (1), Ramile Dilshat (2), Hong Nhung Vu (1), Eiríkur Steingrímsson (1)
Starfsvettvangur / Affiliations: 1. University of Iceland, 2. EMBL Germany
Kynnir / Presenter: Evangeline Breeta Raja David Isac
Melanoma cells are plastic and can change their phenotype from proliferative to migrative cells and vice versa. This behavior means that melanomas can evade drug treatment. The MITF transcription factor has been known to play a vital role in this plasticity. Previous studies from the laboratory have revealed that MITF affects the expression of E-Cadherin (CDH1) and N-Cadherin (CDH2), both of which are involved in epithelial-to-mesenchymal transition (EMT). However, little is known about their role in this transition or their relationship to MITF: Using Cut-and-Run and ChIP-seq data we have identified several MITF-binding peaks containing E-box motifs in the regulatory regions of CDH1. Using transactivation assay in human melanoma cell lines we have shown that MITF activates CDH1 expression through a 1-kb fragment in the intronic region of the gene. Furthermore, transactivation assays and CRISPRi experiments showed that MITF activates CDH1 by binding to particular E-boxes in this regulatory region whereas other E-boxes did not play a role. We are in the process of generating a reporter vector using this MITF regulated region of CDH1 in fusion with eGFP to further characterize its function in phenotype switching.