SUMO2/3 promotes the progression and oxaliplatin resistance of colorectal cancer through facilitating the SUMOylation at Ku80‐K307

Abstract

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide and is typically treated with the FOLFOX regimen (folinic acid, 5‐fluorouracil, and oxaliplatin). However, oxaliplatin resistance remains a serious clinical problem. In the present study, we found that SUMO2/3 was overexpressed in CRC tissues and exogenous overexpression of SUMO2/3 promoted CRC cell proliferation, extension, and invasion and positively regulated the cell cycle. In contrast, SUMO2/3 gene knockdowns inhibited migration and repressed cell viability in vitro and in vivo. In addition, we found that SUMO2/3 was recruited to the cell nucleus and suppressed oxaliplatin‐induced apoptosis of CRC cells. Moreover, Ku80, a DNA‐binding protein essential for the repair of DNA double‐strand breaks, was confirmed to bind with SUMO2/3. Notably, Ku80 undergoes SUMOylation at K307 by SUMO2/3 and this correlated with apoptosis in CRC cells suffering oxaliplatin stress. Collectively, we found that SUMO2/3 plays a specific role in CRC tumorigenesis and acts through Ku80 SUMOylation which is linked with the development of CRC‐oxaliplatin resistance.

FEN1 upregulation mediated by SUMO2 via antagonizing proteasomal degradation promotes hepatocellular carcinoma stemness

“…For instance, SUMO2/3 has been identified as a catalyst for gastric cancer progression, acting through the modulation of NSUN2 stability and its nuclear translocation [55] . Additionally, literature cites SUMO2/3 as a pivotal agent driving colorectal cancer progression and oxaliplatin resistance by orchestrating the sumoylation modification of the DNA assembly constituent, Ku80 [56] . Recent revelations align with our experimental evidence, advocating that SUMO2 exerts a positive regulatory influence on hepatocellular carcinoma progression [ 57 , 58 ].…”