Project name: Snail-dependent epithelial splicing regulatory protein 1 (ESRP1) silencing drives malignant transformation of human pulmonary epithelial cells [mRNA]

Description: The significance of epithelial-to-mesenchymal transition (EMT)-inducing transcription factors in the onset of non-small cell lung cancer has not been resolved. Here, we report increased Snail expression in pulmonary premalignant lesions relative to histologically normal-appearing pulmonary epithelium. Utilizing immortalized human pulmonary epithelial cells and isogenic derivatives, we document Snail-dependent anchorage-independent growth of the epithelial cells in vitro, as well as transformation, primary tumor growth, and metastatic behavior in vivo. Epithelial splicing regulatory protein 1 (ESRP1) tumor suppressor silencing was a requirement for Snail-driven transformation in vivo, and we identified ESRP1 loss in Snail-expressing pulmonary premalignant lesions in situ. Snail drives these and other carcinogenic signaling programs in an ALDH+CD44+CD24- pulmonary stem cell subset in which ESRP1 and stemness-repressing micro-RNAs are inhibited.Overall design: Two distinct HBEC cell lines were transduced with a retroviral vector containing human SNAI1 (Snail) cDNA or the empty vector. They were gene expression profiled to determine the impact of ectopic Snail expression on the isogenic epithelial background of the HBECs.

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: Medical

Last updated: 2017-12-15