A03
SLC-regulating E3 ligases as therapeutic targets in AML
Project Summary
Acute myeloid leukemia (AML) is a highly aggressive hematological malignancy with poor survival rates and limited targeted therapies, necessitating novel approaches. Solute Carrier proteins (SLCs) play a key role in cellular metabolism and growth and are often overexpressed in AML, correlating with poor patient outcomes. Given that ubiquitin is a central regulator of SLC abundance and trafficking, this study hypothesizes that targeting ubiquitin-proteasome system (UPS)-related SLC regulators might be more effective and cancer-specific than direct inhibition of specific SLCs. Using CRISPR/Cas9 screens, we identified DCAF7, an E3 ubiquitin ligase, as common regulator of SLC abundance. Available databases moreover suggest DCAF7 to be an AML-specific oncogene, which is in line with our preliminary data on DCAF7 knockout reducing SLC expression and slowing AML proliferation, thus confirming its potential as therapeutic target. Future work will explore the molecular mechanism of SLC regulation by DCAF7, shed light on its impact on AML biology and develop therapeutic strategies to inhibit DCAF7, finally aiming to exploit these findings for AML treatment.
