biostudies-literatureKim MBLRD VANational Cancer InstituteNCI NIH HHSNational Institutes of HealthU.S. Department of Veterans AffairsNIGMS NIH HHS1284-1294https://www.ebi.ac.uk/biostudies/studies/S-EPMC9356980biostudies-literatureUnknown20(8)Caspase 9 undergoes alternative splicing to produce two opposing isoforms: proapoptotic Caspase 9a and pro-survival Caspase 9b (C9b). Previously, our laboratory reported that C9b is expressed in majority of non-small cell lung cancer tumors and directly activates the NF-κB pathway. In this study, the role of C9b in activation of the NF-κB pathway in vivo, lung inflammation and immune responses, and lung tumorigenesis were examined. Specifically, a transgenic mouse model expressing human C9b in the lung pneumocytes developed inflammatory lung lesions, which correlated with enhanced activation of the NF-κB pathway and increased influx of immunosuppressive myeloid-derived suppressor cells in contrast to wild-type mice. C9b mice presented with facial dermatitis, a thickened and disorganized deMolecular cancer research : MCRCaspase 9b Drives Cellular Transformation, Lung Inflammation, and Lung Tumorigenesis.PMC9356980BX001792CA248298I01 BX001792R01 GM137578R37 CA248298IK6 BX004603GM137578IK6BX004603Kim SUram-Tuculescu CPillappa RChalfant CEVu NTWang MHWang XBulut GBKim MfalseCaspase 9b Drives Cellular Transformation, Lung Inflammation, and Lung Tumorigenesis.Caspase 9 undergoes alternative splicing to produce two opposing isoforms: proapoptotic Caspase 9a and pro-survival Caspase 9b (C9b). Previously, our laboratory reported that C9b is expressed in majority of non-small cell lung cancer tumors and directly activates the NF-κB pathway. In this study, the role of C9b in activation of the NF-κB pathway in vivo, lung inflammation and immune responses, and lung tumorigenesis were examined. Specifically, a transgenic mouse model expressing human C9b in the lung pneumocytes developed inflammatory lung lesions, which correlated with enhanced activation of the NF-κB pathway and increased influx of immunosuppressive myeloid-derived suppressor cells in contrast to wild-type mice. C9b mice presented with facial dermatitis, a thickened and disorganized de2022-01-01T00:00:00Z2022 Aug2026-03-27T16:27:01.759Z2025-08-30T03:05:29.008ZS-EPMC93569803541261510.1158/1541-7786.MCR-21-0905