biostudies-literatureUnknown12Zhao QChinese hamster ovary (CHO) cells undergo endoplasmic reticulum stress (ERS) during intensive recombinant protein production, triggering the unfolded protein response (UPR) to balance cell survival and protein output. Nevertheless, key regulatory components of this process remain incompletely characterized. In this study, we demonstrate that Annexin A1 (ANXA1) functions as a UPR suppressor in CHO cells. Employing the PiggyBac transposon system, we generated a stable ANXA1-knockdown cell line exhibiting a 4.5-fold increase in recombinant antibody expression and a 4.2-fold increase in specific productivity. Pharmacological inhibition using AC2-26 similarly enhanced recombinant protein expression in low-productivity cell populations. Mechanistically, ANXA1 depletion remodeled the UPR by activSynthetic and systems biotechnology197-208https://www.ebi.ac.uk/biostudies/studies/S-EPMC12775871biostudies-literatureLeveraging ANXA1 to enhance recombinant protein yields in CHO cells: A UPR-Mediated bioprocessing approach.PMC12775871Wang JNDong YJZhang HJWang TYLu JTAbiti JJia YLHan MMHua ZCGeng SLZhao QQiu LLZhang XWang WWang XYfalseLeveraging ANXA1 to enhance recombinant protein yields in CHO cells: A UPR-Mediated bioprocessing approach.Chinese hamster ovary (CHO) cells undergo endoplasmic reticulum stress (ERS) during intensive recombinant protein production, triggering the unfolded protein response (UPR) to balance cell survival and protein output. Nevertheless, key regulatory components of this process remain incompletely characterized. In this study, we demonstrate that Annexin A1 (ANXA1) functions as a UPR suppressor in CHO cells. Employing the PiggyBac transposon system, we generated a stable ANXA1-knockdown cell line exhibiting a 4.5-fold increase in recombinant antibody expression and a 4.2-fold increase in specific productivity. Pharmacological inhibition using AC2-26 similarly enhanced recombinant protein expression in low-productivity cell populations. Mechanistically, ANXA1 depletion remodeled the UPR by activ2026-01-01T00:00:00Z2026 Jun2026-06-06T12:25:02.785Z2026-05-30T03:10:48.06ZS-EPMC127758714150951110.1016/j.synbio.2025.12.001