CRISPR/Cas9-mediated UBC knockout impairs CD44 expression and reduces the metastatic potential of 23132/87 gastric cancer cells

The polyubiquitin gene UBC plays a central role in maintaining ubiquitin pools, under both basal and stress conditions. Although UBC is implicated in cell proliferation and survival, its role in gastric cancer remains largely unexplored. We generated UBC -knockout ( UBC -KO) clones in the 23132/87 primary gastric cancer cell line via CRISPR/Cas9 to assess the functional impact of UBC on tumor progression. UBC deletion markedly reduced cellular ubiquitin pools and induced proteasome remodeling, characterized by β5i (PSMB8) upregulation and incorporation into ubiquitin-independent proteasome complexes. Transcriptomic profiling revealed extensive changes in gene expression in UBC -deficient cells affecting pathways related to cell adhesion, protein homeostasis and cell apoptosis. Notably, UBC -KO clones exhibited an almost complete abrogation of CD44 expression, a known gastric cancer marker, and the downregulation of pro-metastatic drivers such as LGALS4 and Claudin-1. This transcriptional rewiring translated into reduced proliferation, impaired migratory and invasive capabilities. Our study identifies UBC as a pivotal regulator of ubiquitin availability that links proteostasis with transcriptional reprogramming regulating tumor aggressiveness. These findings reveal a link between UBC and CD44-mediated gastric cancer progression, highlighting UBC as a novel therapeutic target in this malignancy.