Functional significance of Rpn10. (A) Dependency scores of Rpn10 across cancers based on CRISPR data sets in the DepMap web portal. A lower chronos score indicates that the gene of interest is essential in a given cell line. Score 0 means the gene is not essential, whereas score –1 is comparable with the median of all panessential genes (red line). (B) The proliferation of the MM.1S and ANBL6 inducible Rpn10-shRNA KD cell lines were analyzed using a CTG assay (mean ± SD, n = 3) when cultured with or without Dox. Inducible KD of Rpn10 was achieved using pTRIPz-mCherry vector containing Rpn10-shRNA or scramble control. (C) The stable adding back cell line was achieved when AMO1 Rpn10-iKO cells were transfected with lentivirus-packaged V5-tagged Rpn10 plasmid or empty plasmid (pEV), followed by blasticidin selection. Cell proliferation was measured by a CTG assay (mean ± SD, n = 3). Immunoblot shows the expression levels of Rpn10. Human AMO1 Rpn10-shRNA KD cells (D) or MM.1S Rpn10-shRNA KD cells (E-F) were subcutaneously inoculated into CB17 severe combined immunodeficiency mice. In the early prevention model (D-E), a cohort of mice was treated with an irradiated 0.0625% Dox diet (1-6 mg of Dox per mouse per day) continuously starting 5 days after injection. In the late prevention model (n = 10) (F), mice were treated with an irradiated 0.0625% Dox diet after the tumor became visible and the volume was ∼100 mm³. The average and standard deviation of tumor volume (mm³) are shown vs the time when the tumor was measured (mean tumor volume ± SD). Kaplan-Meier plots show survival in mice (right). Internal blot shows Rpn10 expression of the tumor lysates.