DCAF12 Ubiquitin Ligase Promotes Lung Cancer Metastasis by Modulating the TRiC/CCT Chaperonin Complex.

ABSTRACT: Metastasis is the primary challenge in lung cancer treatment. Although proteostasis supports tumor growth, the mechanism by which ubiquitin ligases reprogram chaperone networks to drive metastasis is poorly understood. In this study, it is revealed that DDB1-CUL4-associated factor (DCAF12), a substrate receptor for CUL4-RING ubiquitin ligases, regulates metastatic progression through ubiquitin-mediated proteostatic reprogramming. DCAF12 depletion suppresses tumor cell migration and stemness in vitro and reduces pulmonary/hepatic metastasis in vivo. Mechanistically, DCAF12 catalyzes the non-degradative ubiquitination of TRiC/CCT subunits, enhancing chaperonin assembly and folding of cytoskeletal effectors (β-actin/tubulin) and oncogenic clients (STAT3/Raptor/mLST8), thereby activating the Y

SUBMITTER: Wang Z 

PROVIDER: S-EPMC12806248 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature