A TNFR1-UBCH10 axis drives lung squamous cell carcinoma dedifferentiation and metastasis through a cell-autonomous signaling loop.

ABSTRACT: Tumor necrosis factor receptor 1 (TNFR1), encoded by TNFRSF1A, is a critical transducer of inflammatory pathways, but its physiological role in human cancer is not completely understood. Here, we observed high expression of TNFR1 in many human lung squamous cell carcinoma (SCCs) samples and in spontaneous lung SCCs derived from kinase-dead Ikkα knock-in (KA/KA) mice. Knocking out Tnfrf1a in KA/KA mice blocked lung SCC formation. When injected via tail vein, KAL^LU+ lung SCC cells that highly expressed TNFR1/TNF, Sox2, c-Myc, Twist1, Bcl2, and UBCH10, generated dedifferentiated spindle cell carcinomas with epithelial-mesenchymal transition markers in mouse lungs. In contrast, KAL^LU+ cells with silenced TNFR1 and KAL^LU- cells that expressed low levels of TNFR1

SUBMITTER: Xiao Z 

PROVIDER: S-EPMC9587052 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature