UBC9-mediated SUMOylation of CORO1C drives lung adenocarcinoma progression via Arp2/3-dependent cytoskeletal remodeling.

Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality worldwide, and understanding its molecular drivers is critical for improving therapeutic outcomes. SUMOylation is a form of post-translational modification that conjugates small ubiquitin-like modifier (SUMO) to specific lysine residues of target proteins. The sole SUMO E2-conjugating enzyme UBC9 is upregulated in multiple malignancies, yet its functional role and specific substrate in LUAD remain poorly defined. Here, we demonstrate that UBC9 is significantly elevated in LUAD tissues, and its high expression is associated with adverse clinic outcomes. Functional assays revealed that genetic ablation of UBC9 robustly suppresses LUAD cell proliferation, migration, invasion, and tumorigenesis both in vitro and in vivo. Through immunoprecipitation-mass spectrometry, we identified Coronin-1C (CORO1C), a master regulator of actin dynamics, as a key substrate of UBC9-mediated SUMOylation. Mechanistically, SUMOylation of CORO1C at lysine residues K19, K311, and K440 enhances its binding to actin-related protein 2 (Arp2) complex, promotes actin‑based cytoskeletal remodeling, and drives malignant cellular behaviors. Collectively, our work reveals a previously unrecognized regulatory axis in which UBC9‑dependent SUMOylation licenses CORO1C to orchestrate Arp2/3‑mediated cytoskeletal dynamics, thereby advancing LUAD progression. These findings reveal CORO1C as a novel SUMOylation target in lung adenocarcinoma and offer new mechanistic insights into tumor cell motility, but also highlight a promising therapeutic avenue for treating advanced LUAD.