LUBAC determines chemotherapy resistance in squamous cell lung cancerMore about Open Access at the Crick
Authors listJosue Ruiz Markus E Diefenbacher Jessica Nelson Rocio Sancho Fabio Pucci Atanu Chakraborty Paula Moreno Alessandro Annibaldi Gianmaria Liccardi Vesela Encheva Richard Mitter Mathias Rosenfeldt Bram Snijders Pascal Meier Marco A Calzado Axel Behrens
Lung squamous cell carcinoma (LSCC) and adenocarcinoma (LADC) are the most common lung cancer subtypes. Molecular targeted treatments have improved LADC patient survival but are largely ineffective in LSCC. The tumor suppressor FBW7 is commonly mutated or down-regulated in human LSCC, and oncogenic KRasG12D activation combined with Fbxw7 inactivation in mice (KF model) caused both LSCC and LADC. Lineage-tracing experiments showed that CC10+, but not basal, cells are the cells of origin of LSCC in KF mice. KF LSCC tumors recapitulated human LSCC resistance to cisplatin-based chemotherapy, and we identified LUBAC-mediated NF-κB signaling as a determinant of chemotherapy resistance in human and mouse. Inhibition of NF-κB activation using TAK1 or LUBAC inhibitors resensitized LSCC tumors to cisplatin, suggesting a future avenue for LSCC patient treatment.
Journal Journal of Experimental Medicine
Issue number 2