Genetic disruption ofUSP9Xsensitizes colorectal cancer cells to 5-fluorouracil

Context-dependent function of the deubiquitinating enzyme USP9X in pancreatic ductal adenocarcinoma

“…In this regard, USP9X inhibition has been shown to enhance the effects of SAHA and 5-FU, 3 and USP9X increases radio-resistance by stabilizing MCL1. 37 Moreover, small molecule inhibitors of ubiquitin specific peptidases have been developed, including WP1130 23 and HBX41108.…”

“…2 Knockdown of USP9X in the context of colorectal carcinoma leads to increased activity of pro-apoptotic pathways and increased sensitivity to the cytotoxic effects of 5-fluorouracil. 3 In the context of prostate cancer, USP9X stabilizes the oncogenic transcription factor ERG, and disruption of USP9X by the deubiquitinating protease inhibitor, WP1130, inhibited prostate tumor cell growth in mice. 4 Moreover, knockdown of USP9X in medulloblastoma and glioblastoma cells dramatically impairs their growth.…”

The Deubiquitinase USP9X Maintains DNA Replication Fork Stability and DNA Damage Checkpoint Responses by Regulating CLASPIN during S-Phase

“…Increased DNA damage and a diminished ability to promote efficient checkpoint signaling may also be the reason for the hypersensitivity to other genotoxic agents such 5-fluorouracil in USP9X-deficient colorectal cancer cells (48).…”

Targeting deubiquitinase activity with a novel small-molecule inhibitor as therapy for B-cell malignancies

“…5 Usp9x was also recently shown to suppress chemotherapy, radiotherapy, and targeted therapy in several tumor types through its regulation of Mcl-1 and other proteins. 6,7 Mcl-1 is essential for tumor cell survival, and high levels are noted in patients with drug-resistant MM. 8 By using proteomics, ubiquitinated Mcl-1 was recently shown to be bound and deubiquitinated by Usp9x, thus preventing its destruction by the proteasome.…”