RT Journal Article
T1 LUBAC determines chemotherapy resistance in squamous cell lung cancer.
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
AB 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.
PB Rockefeller University Press
YR 2018
FD 2018-12-18
LK http://hdl.handle.net/10668/13422
UL http://hdl.handle.net/10668/13422
LA en
NO Ruiz EJ, Diefenbacher ME, Nelson JK, Sancho R, Pucci F, Chakraborty A, et al. LUBAC determines chemotherapy resistance in squamous cell lung cancer. J Exp Med. 2019 Feb 4;216(2):450-465
DS RISalud
RD Apr 20, 2025