hnRNP A2/B1 Modulates Epithelial-Mesenchymal Transition in Lung Cancer Cell Lines

• Published in: Cancer research (Chicago, Ill.) Vol. 70; no. 18; pp. 7137 - 7147
• Main Authors: TAULER, Jordi, ZUDAIRE, Enrique, LIU, Huaitian, SHIH, Joanna, MULSHINE, James L
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.09.2010
• Subjects: Antineoplastic agents; Biological and medical sciences; Cadherins - antagonists & inhibitors; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell Growth Processes - physiology; Cell Line, Tumor; Cell Movement - physiology; Epithelial Cells - pathology; Gene Silencing; Heterogeneous-Nuclear Ribonucleoprotein Group A-B - biosynthesis; Heterogeneous-Nuclear Ribonucleoprotein Group A-B - genetics; Humans; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Medical sciences; Mesoderm - pathology; Nuclear Proteins - biosynthesis; Pharmacology. Drug treatments; Pneumology; Snail Family Transcription Factors; Transcription Factors - biosynthesis; Tumors; Tumors of the respiratory system and mediastinum; Twist-Related Protein 1 - biosynthesis; Lung disease; Respiratory disease; Lung cancer; Established cell line; Bronchus disease; Malignant tumor; Mesenchymal cell; In vitro; Bronchopulmonary; Tumor cell; Cancer
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-10-0860

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) has been reported to be overexpressed in lung cancer and in other cancers such as breast, pancreas, and liver. However, a mechanism linking hnRNP A2/B1 overexpression and progression to cancer has not yet been definitively established. To elucidate this mechanism, we have silenced hnRNPA2/B1 mRNA in non-small-cell lung cancer cell lines A549, H1703, and H358. These cell lines present different levels of expression of epithelial-to-mesenchymal transition (EMT) markers such as E-cadherin, fibronectin, and vimentin. Microarray expression analysis was performed to evaluate the effect of silencing hnRNP A2/B1 in A549 cells. We identified a list of target genes, affected by silencing of hnRNP A2/B1, that are involved in regulation of migration, proliferation, survival, and apoptosis. Silencing hnRNP A2/B1 induced formation of cell clusters and increased proliferation. In the anchorage-independent assay, silencing hnRNP A2/B1 increased colony formation by 794% in A549 and 174% in H1703 compared with a 25% increase in proliferation, in both cell lines, in a two-dimensional proliferation assay. Silencing hnRNP A2/B1 decreased migration in intermediate cell line A549 and mesenchymal cell line H1703; however, no changes in proliferation were observed in epithelial cell line H358. Silencing hnRNP A2/B1 in A549 and H1703 cells correlated with an increase of E-cadherin expression and downregulation of the E-cadherin inhibitors Twist1 and Snai1. These data suggest that expression of hnRNP A2/B1 may play a role in EMT, in nonepithelial lung cancer cell lines A549 and H1703, through the regulation of E-cadherin expression.