Molecular portraits of epithelial, mesenchymal, and hybrid States in lung adenocarcinoma and their relevance to survival

Epithelial-to-mesenchymal transition (EMT) is a key process associated with tumor progression and metastasis. To define molecular features associated with EMT states, we undertook an integrative approach combining mRNA, miRNA, DNA methylation, and proteomic profiles of 38 cell populations representa...

Full description

Saved in:

Bibliographic Details
Published in:	Cancer research (Chicago, Ill.) Ill.), 2015-05, Vol.75 (9), p.1789-1800
Main Authors:	Schliekelman, Mark J, Taguchi, Ayumu, Zhu, Jun, Dai, Xudong, Rodriguez, Jaime, Celiktas, Muge, Zhang, Qing, Chin, Alice, Wong, Chee-Hong, Wang, Hong, McFerrin, Lisa, Selamat, Suhaida A, Yang, Chenchen, Kroh, Evan M, Garg, Kavita S, Behrens, Carmen, Gazdar, Adi F, Laird-Offringa, Ite A, Tewari, Muneesh, Wistuba, Ignacio I, Thiery, Jean P, Hanash, Samir M
Format:	Article
Language:	eng
Subjects:	Adenocarcinoma - genetics Adenocarcinoma - metabolism Adenocarcinoma - pathology Adenocarcinoma of Lung Cadherins - metabolism Cell Adhesion - genetics Cell Line, Tumor Cell Movement - genetics Cell Survival - genetics Cell Survival - physiology Cytoskeleton - metabolism DNA Methylation Epithelial Cells - metabolism Epithelial Cells - pathology Epithelial-Mesenchymal Transition - genetics Epithelial-Mesenchymal Transition - physiology Humans Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - pathology Microfilament Proteins - metabolism MicroRNAs - genetics Proteomics - methods Transforming Growth Factor beta - metabolism Up-Regulation Vimentin - metabolism
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Epithelial-to-mesenchymal transition (EMT) is a key process associated with tumor progression and metastasis. To define molecular features associated with EMT states, we undertook an integrative approach combining mRNA, miRNA, DNA methylation, and proteomic profiles of 38 cell populations representative of the genomic heterogeneity in lung adenocarcinoma. The resulting data were integrated with functional profiles consisting of cell invasiveness, adhesion, and motility. A subset of cell lines that were readily defined as epithelial or mesenchymal based on their morphology and E-cadherin and vimentin expression elicited distinctive molecular signatures. Other cell populations displayed intermediate/hybrid states of EMT, with mixed epithelial and mesenchymal characteristics. A dominant proteomic feature of aggressive hybrid cell lines was upregulation of cytoskeletal and actin-binding proteins, a signature shared with mesenchymal cell lines. Cytoskeletal reorganization preceded loss of E-cadherin in epithelial cells in which EMT was induced by TGFβ. A set of transcripts corresponding to the mesenchymal protein signature enriched in cytoskeletal proteins was found to be predictive of survival in independent datasets of lung adenocarcinomas. Our findings point to an association between cytoskeletal and actin-binding proteins, a mesenchymal or hybrid EMT phenotype and invasive properties of lung adenocarcinomas.
ISSN:	0008-5472 1538-7445