TY  - JOUR
A1  - Ruiz, E. Josue
A1  - Diefenbacher, Markus E.
A1  - Nelson, Jessica K.
A1  - Sancho, Rocio
A1  - Pucci, Fabio
A1  - Chakraborty, Atanu
A1  - Moreno, Paula
A1  - Annibaldi, Alessandro
A1  - Liccardi, Gianmaria
A1  - Encheva, Vesela
A1  - Mitter, Richard
A1  - Rosenfeldt, Mathias
A1  - Snijders, Ambrosius P.
A1  - Meier, Pascal
A1  - Calzado, Marco A.
A1  - Behrens, Axel
T1  - LUBAC determines chemotherapy resistance in squamous cell lung cancer
JF  - Journal of Experimental Medicine
N2  - 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-kappa B signaling as a determinant of chemotherapy resistance in human and mouse. Inhibition of NF-kappa B activation using TAK1 or LUBAC inhibitors resensitized LSCC tumors to cisplatin, suggesting a future avenue for LSCC patient treatment.
KW  - Solid tumors
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227146
VL  - 216
IS  - 2
ER  -