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SLC-regulating E3 ligases as therapeutic targets in AML (A03)

Subject Area Hematology, Oncology
Term since 2024
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 514894665
 
Solute carrier proteins (SLCs) such as SLC1A5 (ASCT2) and SLC16A1 (MCT1) are often overexpressed in AML. Searching for underlying regulators, we performed focused CRISPR screens and identified the E3 ligases SIAH1 and DCAF7 as common opposite regulators of both SLCs. Overexpression of SIAH1 and loss of DCAF7 reduced SLC abundance and proliferation in AML cells, and correlated with improved patient outcome, suggesting tumor-suppressor and oncogenic roles respectively. We hence aim to establish SIAH1 and DCAF7 as SLC regulators and therapeutic targets in AML and develop means to stabilize SIAH1 or inhibit DCAF7 with the help of this consortium.
DFG Programme CRC/Transregios
 
 

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