The role of deubiquitinating enzyme USP17 in non-small cell lung cancer as a potential therapeutic target

USP17 has been shown to regulate cell cycle progression, lysosomal trafficking, and epithelial-to- mesenchymal transition (EMT), and its expression has been associated with cancer progression and reduced progression free survival. Depletion of USP17 is reported to reduce non-small cell lung cancer (NSCLC) tumourigenesis and enhance sensitivity to first line tyrosine-kinase inhibitors.<br><br>Chapter 3 investigates USP17’s impact on NSCLC growth in 3D in vitro studies, and the cellular impact of its phosphorylation at S41.

USP17 expression increases A549 colony formation in 3D clonogenic assays, which is dependent on its deubiquitinating activity and phosphorylation at S41. Similarly, USP17 depletion reduces A549 colony formation. Additionally, USP17 drives EMT and protease secretion via lysosomal exocytosis in NSCLC, regardless of the phosphorylation status at S41.<br><br>Chapter 4 investigates USP17’s impact on gefitinib sensitivity of EGFR mutant (mtEGFR) NSCLC using 3D spheroid in vitro models.