NRF3 suppresses squamous carcinogenesis, involving the unfolded protein response regulator HSPA5

ABSTRACT: Epithelial skin cancers are extremely common, but the mechanisms underlying their malignant progression are still poorly defined. Here we identify the NRF3 transcription factor as a tumor suppressor in the skin. NRF3 protein expression is strongly down-regulated or even absent in invasively growing cancer cells of patients with basal and squamous cell carcinomas (BCC and SCC). NRF3 deficiency promoted malignant conversion of chemically-induced skin tumors in immunocompetent mice, clonogenic growth and migration of human SCC cells, their invasiveness in 3D cultures, and xenograft tumor formation. Mechanistically, the tumor-suppressive effect of NRF3 involves HSPA5, a key regulator of the unfolded protein response, which we identified as a potential NRF3 interactor. HSPA5 levels increased in

SUBMITTER: Mrs. Selina Gurri 

PROVIDER: S-SCDT-10_15252-EMMM_202317761 | biostudies-other |

REPOSITORIES: biostudies-other