biostudies-literatureUnknownWang XNCI NIH HHSCytosolic arginine sensor for mTORC1 Subunit 1 (CASTOR1) functions as a key regulator of mechanistic target of rapamycin complex 1 (mTORC1) signaling. Despite its frequent dysregulation in cancers via mechanisms such as KSHV microRNA-mediated inhibition or AKT-driven phosphorylation and degradation, the impact of CASTOR1 loss on tumor initiation and progression remains poorly understood. Here, we identify CASTOR1 as a critical tumor suppressor in non-small cell lung cancer (NSCLC) by demonstrating that its genetic ablation amplifies tumorigenesis in a KRAS-driven genetically engineered mouse model (GEMM;LSL-KRAS G12D). CASTOR1 deficiency markedly enhances lung tumor incidence, accelerates tumor progression, and increases proliferative indices ibioRxiv : the preprint server for biology2025.04.23.650349https://www.ebi.ac.uk/biostudies/studies/S-EPMC12045348biostudies-literatureCASTOR1: A Novel Tumor Suppressor Linking mTORC1 and KRAS Pathways in Tumorigenesis and Resistance to KRAS-Targeted Therapies in Non-Small Cell Lung Cancer.PMC12045348P30 CA047904R01 CA124332R01 CA291244R01 CA284554R01 CA096512R01 CA278812Loo SKGao SJHuang YLi TWang MTSun SChen LPennathur AWang XDing LfalseCASTOR1: A Novel Tumor Suppressor Linking mTORC1 and KRAS Pathways in Tumorigenesis and Resistance to KRAS-Targeted Therapies in Non-Small Cell Lung Cancer.Cytosolic arginine sensor for mTORC1 Subunit 1 (CASTOR1) functions as a key regulator of mechanistic target of rapamycin complex 1 (mTORC1) signaling. Despite its frequent dysregulation in cancers via mechanisms such as KSHV microRNA-mediated inhibition or AKT-driven phosphorylation and degradation, the impact of CASTOR1 loss on tumor initiation and progression remains poorly understood. Here, we identify CASTOR1 as a critical tumor suppressor in non-small cell lung cancer (NSCLC) by demonstrating that its genetic ablation amplifies tumorigenesis in a KRAS-driven genetically engineered mouse model (GEMM;LSL-KRAS G12D). CASTOR1 deficiency markedly enhances lung tumor incidence, accelerates tumor progression, and increases proliferative indices i2025-01-01T00:00:00Z2025 Apr2026-06-30T03:26:21.731Z2026-06-30T03:21:01.032ZS-EPMC120453484031392410.1101/2025.04.23.650349