Publicaciones científicas

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

18-dic-2018 | Revista: 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).


RESUMEN

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.

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

Nuestros autores

Inés López Erdozain
Elizabet Guruceaga Martínez
Técnico de Investigación Bioinformático Plataforma Bioinformática
Iosune Baraibar Argota
Margarita Ecay Ilzarbe
Técnico de laboratorio Plataforma de Micro-PET
Adrián Vallejo Blanco
Graduado Adscrito a Proyecto Programa de Investigación en Tumores Sólidos
Dr. Patxi San Martín Uriz
Investigador Adscrito a Proyecto Grupo de Investigación en Hematología Traslacional