The inhibitor of differentiation-1 (Id1) enables lung cancer liver colonization through activation of an EMT program in tumor cells and establishment of the pre-metastatic niche

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RESEARCH PRODUCT

The inhibitor of differentiation-1 (Id1) enables lung cancer liver colonization through activation of an EMT program in tumor cells and establishment of the pre-metastatic niche

Ignacio Gil-bazo Christian Rolfo Walter Weder Fernando Vidal-vanaclocha Eduardo Castanon Alfonso Calvo María Collantes Inés López Iosune Baraibar Miriam Redrado Margarita Ecay Marta Roman José María López-picazo Alex Soltermann Luis E. Raez

subject

Inhibitor of Differentiation Protein 1 0301 basic medicine Cancer Research Pathology Lung Neoplasms Time Factors 10255 Clinic for Thoracic Surgery Vimentin medicine.disease_cause Metastasis Carcinoma Lewis Lung 0302 clinical medicine Cell Movement Carcinoma Non-Small-Cell Lung Tumor Microenvironment 1306 Cancer Research Mice Knockout Tissue microarray Integrin beta1 Liver Neoplasms Tumor Burden Gene Expression Regulation Neoplastic Oncology 030220 oncology & carcinogenesis 2730 Oncology Signal Transduction medicine.medical_specialty Epithelial-Mesenchymal Transition Liver tumor 610 Medicine & health Biology Transforming Growth Factor beta1 03 medical and health sciences Cell Line Tumor 10049 Institute of Pathology and Molecular Pathology medicine Animals Humans Vimentin Epithelial–mesenchymal transition Lung cancer Cell Proliferation Lewis lung carcinoma medicine.disease Mice Inbred C57BL 030104 developmental biology Cancer research biology.protein Human medicine Snail Family Transcription Factors Carcinogenesis

description

Abstract: Id1 promotes carcinogenesis and metastasis, and predicts prognosis of non-small cell lung cancer (NSCLC)-adenocarcionoma patients. We hypothesized that Id1 may play a critical role in lung cancer colonization of the liver by affecting both tumor cells and the microenvironment. Depleted levels of Id1 in LLC (Lewis lung carcinoma cells, LLC shId1) significantly reduced cell proliferation and migration in vitro. Genetic loss of Id1 in the host tissue (Id1(-/-) mice) impaired liver colonization and increased survival of Id1 animals. Histologically, the presence of Idl in tumor cells of liver metastasis was responsible for liver colonization. Microarray analysis comparing liver tumor nodules from Id1(+/+) mice and Idl(-/-) mice injected with LLC control cells revealed that Id1 loss reduces the levels of EMT-related proteins, such as vimentin. In tissue microarrays containing 532 NSCLC patients' samples, we found that Idl significantly correlated with vimentin and other EMT-related proteins. Idl loss decreased the levels of vimentin, integrin beta 1, TGF beta 1 and snail, both in vitro and in vivo. Therefore, Id1 enables both LLC and the host microenvironment for an effective liver colonization, and may represent a novel therapeutic target to avoid NSCLC liver metastasis. (C) 2017 Elsevier B.V. All rights reserved.

year	journal	country	edition	language
2017-05-24	Cancer Letters

https://doi.org/10.1016/j.canlet.2017.05.012