Scientific publications

Inhibitor of differentiation-1 (Id1) sustains mutant KRAS-driven progression, maintenance, and metastasis of lung adenocarcinoma via regulation of a FOSL1 network

Dec 18, 2018 | Magazine: Cancer Research

Román M (1), López I (1), Guruceaga E (2), Baraibar I (3), Ecay M (4), Collantes M (4), Nadal E (5), Vallejo A (1), Cadenas S (6), Echávarri-de Miguel M (6), Jang JH (7), San Martín-Uriz P (8), Castro-Labrador L (9), Vilas-Zornoza A (10), Lara-Astiaso D (11), Ponz-Sarvise M (12), Rolfo C (13), Santos ES (14), Raez LE (15), Taverna S (16), Behrens C (17), Weder W (18), Wistuba II (19), Vicent S (20), Gil-Bazo I (21).


Due to the refractory nature of mutant KRAS lung adenocarcinoma (LUAD) to current therapies, identification of new molecular targets is essential.

Genes with a prognostic role in mutant KRAS LUAD have proven to be potential molecular targets for therapeutic development. Here we determine the clinical, functional, and mechanistic role of inhibitor of differentiation-1 (Id1) in mutant KRAS LUAD.

Analysis of LUAD cohorts from TCGA and SPORE showed that high expression of Id1 was a marker of poor survival in patients harboring mutant, but not wild-type KRAS. Abrogation of Id1 induced G2/M arrest and apoptosis in mutant KRAS LUAD cells.

In vivo, loss of Id1 strongly impaired tumor growth and maintenance as well as liver metastasis, resulting in improved survival. Mechanistically, Id1 was regulated by the KRAS oncogene through JNK, and loss of Id1 resulted in downregulation of elements of the mitotic machinery via inhibition of the transcription factor FOSL1 and of several kinases within the KRAS signaling network.

Our study provides clinical, functional, and mechanistic evidence underscoring Id1 as a critical gene in mutant KRAS LUAD and warrants further studies of Id1 as a therapeutic target in LUAD patients.

CITATION  Cancer Res. 2019 Feb 1;79(3):625-638.
doi: 10.1158/0008-5472.CAN-18-1479. Epub 2018 Dec 18

Our authors

Elizabet Guruceaga Martínez
Bioinformatics Research Technician Bioinformatics Platform
Iosune Baraibar Argota
Margarita Ecay Ilzarbe
Laboratory technician Micro-PET Platform
Adrián Vallejo Blanco
Project Graduate Solid Tumor Research Program
Dr. Patxi San Martín Uriz