LUBAC determines chemotherapy resistance in squamous cell lung cancer

E Josue Ruiz; Markus E Diefenbacher; Jessica K Nelson; Rocio Sancho; Fabio Pucci; Atanu Chakraborty; Paula Moreno; Alessandro Annibaldi; Gianmaria Liccardi; Vesela Encheva; Richard Mitter; Mathias Rosenfeldt; Ambrosius P Snijders; Pascal Meier; Marco A Calzado; Axel Behrens

doi:10.1084/jem.20180742

LUBAC determines chemotherapy resistance in squamous cell lung cancer

E Josue Ruiz, Markus E Diefenbacher, Jessica K Nelson, Rocio Sancho, Fabio Pucci, Atanu Chakraborty, Paula Moreno, Alessandro Annibaldi, Gianmaria Liccardi, Vesela Encheva, Richard Mitter, Mathias Rosenfeldt, Ambrosius P Snijders, Pascal Meier, Marco A Calzado, Axel Behrens

Unidad de Cirugía Torácica y Trasplante Pulmonar, Hospital Universitario Reina Sofía, Córdoba, Spain.
Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, London SW3 6JB, UK.
University of Würzburg, Comprehensive Cancer Center Mainfranken, Würzburg, Germany.
Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Córdoba, Spain.
Francis Crick Institute
Schools of Life Course Sciences & Population Health and Environmental Sciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.

Research output: Contribution to journal › Article › peer-review

61 Citations (Scopus)

131 Downloads (Pure)

Abstract

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.

Original language	English
Pages (from-to)	450-465
Number of pages	16
Journal	The Journal of experimental medicine
Volume	216
Issue number	2
Early online date	14 Jan 2019
DOIs	https://doi.org/10.1084/jem.20180742
Publication status	Published - 4 Feb 2019

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1084/jem.20180742Licence: CC BY

LUBAC determines chemotherapy resistance_RUIZ_Accepted 18 December 2018_GOLD VoR (CC BY)Final published version, 3.98 MBLicence: CC BY

Cite this

Ruiz, E. J., Diefenbacher, M. E., Nelson, J. K., Sancho, R., Pucci, F., Chakraborty, A., Moreno, P., Annibaldi, A., Liccardi, G., Encheva, V., Mitter, R., Rosenfeldt, M., Snijders, A. P., Meier, P., Calzado, M. A., & Behrens, A. (2019). LUBAC determines chemotherapy resistance in squamous cell lung cancer. The Journal of experimental medicine, 216(2), 450-465. https://doi.org/10.1084/jem.20180742

@article{4f2e1fdf578d45a8a0305f242443407d,

title = "LUBAC determines chemotherapy resistance in squamous cell lung cancer",

abstract = "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.",

author = "Ruiz, {E Josue} and Diefenbacher, {Markus E} and Nelson, {Jessica K} and Rocio Sancho and Fabio Pucci and Atanu Chakraborty and Paula Moreno and Alessandro Annibaldi and Gianmaria Liccardi and Vesela Encheva and Richard Mitter and Mathias Rosenfeldt and Snijders, {Ambrosius P} and Pascal Meier and Calzado, {Marco A} and Axel Behrens",

note = "{\textcopyright} 2019 Ruiz et al.",

year = "2019",

month = feb,

day = "4",

doi = "10.1084/jem.20180742",

language = "English",

volume = "216",

pages = "450--465",

journal = "The Journal of experimental medicine",

issn = "0022-1007",

publisher = "Rockefeller University Press",

number = "2",

}

Ruiz, EJ, Diefenbacher, ME, Nelson, JK, Sancho, R, Pucci, F, Chakraborty, A, Moreno, P, Annibaldi, A, Liccardi, G, Encheva, V, Mitter, R, Rosenfeldt, M, Snijders, AP, Meier, P, Calzado, MA & Behrens, A 2019, 'LUBAC determines chemotherapy resistance in squamous cell lung cancer', The Journal of experimental medicine, vol. 216, no. 2, pp. 450-465. https://doi.org/10.1084/jem.20180742

TY - JOUR

T1 - LUBAC determines chemotherapy resistance in squamous cell lung cancer

AU - Ruiz, E Josue

AU - Diefenbacher, Markus E

AU - Nelson, Jessica K

AU - Sancho, Rocio

AU - Pucci, Fabio

AU - Chakraborty, Atanu

AU - Moreno, Paula

AU - Annibaldi, Alessandro

AU - Liccardi, Gianmaria

AU - Encheva, Vesela

AU - Mitter, Richard

AU - Rosenfeldt, Mathias

AU - Snijders, Ambrosius P

AU - Meier, Pascal

AU - Calzado, Marco A

AU - Behrens, Axel

PY - 2019/2/4

Y1 - 2019/2/4

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-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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85061140162&partnerID=8YFLogxK

U2 - 10.1084/jem.20180742

DO - 10.1084/jem.20180742

M3 - Article

C2 - 30642944

SN - 0022-1007

VL - 216

SP - 450

EP - 465

JO - The Journal of experimental medicine

JF - The Journal of experimental medicine

IS - 2

ER -

LUBAC determines chemotherapy resistance in squamous cell lung cancer

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this