Chronic inflammation induces epithelial-to-mesenchymal transition memory in non-small cell lung cancer

GSE142620 Chronic inflammation induces epithelial-to-mesenchymal transition memory in non-small cell lung cancer: Contributors : Rui Li ; Stephanie L Ong ; Linh M Tran ; Zhe Jing ; Zhi L Huang ; Bin Liu ; Gina Lee ; Ramin Salehi-Rad ; Kostyantyn Krysan ; Paul C Pagano ; Manash K Paul ; Shili Xu ; Harvey R Herschman ; Steven M Dubinett

Series Type : Expression profiling by high throughput sequencing

Organism : Homo sapiens

Chronic inflammation facilitates tumor development. However, the underlying mechanism is largely unknown. Here, we found IL-1β, a critical cytokine in lung tumor progression, induces epithelial-to-mesenchymal (EMT) in non-small cell lung cancer (NSCLC) cells. Chronic IL-1β exposure leads to “EMT memory,” a prolonged EMT program in the absence of the original inflammatory stimulus. The transcription factor SNAI2 is indispensable for the establishment of EMT phenotypes. However, SNAI2 is not required to maintain EMT memory once it is established. A temporal regulation of epigenetic modifications, including histone modifications and DNA methylation, drives the downregulation of E-cadherin in IL-1β-induced EMT. Inhibition of DNA methylation not only reverses EMT memory, but also primes these mesenchymal cells for chemotherapy-induced apoptosis. These findings enhance our understanding of the molecular events bridging acute to chronic inflammation and reveal epigenetic modifications as a potential mechanism for temporal-spatial regulation of EMT during metastasis