Ixazomib triggers autophagic degradation of MUC5AC/integrin-β4 and inhibits non-small cell lung cancer progression - PubMed
4 hours ago
- #Lung Cancer
- #Autophagy
- #Proteasome Inhibition
- Ixazomib (IXZ) identified as a potential agent against lung adenocarcinoma (LUAD) through connectivity mapping analysis.
- IXZ inhibits LUAD cell growth, induces G2/M arrest, and promotes cell death, both alone and in combination with carboplatin (CBP).
- IXZ induces DNA damage and attenuates repair mechanisms in cisplatin-resistant cells, suggesting a role in overcoming platinum resistance.
- IXZ degrades MUC5AC/integrin-β4 via the ubiquitin-mediated autophagy pathway, as shown by reporter assays and pathway interventions.
- IXZ destabilizes MUC5AC by blocking interaction with the deubiquitinase UCHL1.
- In vivo studies demonstrate IXZ significantly decreases tumor burden by blocking the MUC5AC/UCHL1 oncogenic axis.
- IXZ may overcome platinum resistance, warranting further clinical investigation in LUAD patients.