Targeting heat shock protein 90 with usnic acid relieves immune suppression via aryl hydrocarbon receptor-mediated mechanisms in lung cancer.

ABSTRACT: Immune evasion in lung cancer is closely associated with the dysregulation of molecular chaperones and immunoregulatory pathways. Heat shock protein 90 (HSP90), which is frequently overexpressed in lung cancer and correlates with poor prognosis, has emerged as a promising therapeutic target. Here, we investigated whether targeting the HSP90-aryl hydrocarbon receptor (AhR) axis with usnic acid (UA) could suppress immune evasion mechanisms in lung cancer. Through target prediction and molecular docking, UA-bead-based proteomic profiling, and in vitro assays, we identified HSP90 as a direct binding of UA. Unlike classical HSP90 inhibitors, UA downregulates HSP90 protein level and disrupts the HSP90-AhR complex, thereby promoting proteasomal degradation of AhR and reducing its half-life. This

SUBMITTER: Varlı M 

PROVIDER: S-EPMC12528611 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature