<i>UBAP2L</i> is amplified in a large subset of human lung adenocarcinoma and is critical for epithelial lung cell identity and tumor metastasis

Abstract

The ubiquitin-associated protein 2-like (<i>UBAP2L</i>) gene remains poorly studied in human and mouse development. UBAP2L interacts with the Polycomb group protein B lymphoma Mo-MLV insertion region 1 homolog (BMI1) and determines the activity of mouse hematopoietic stem cells <i>in vivo</i> Here we show that loss of <i>Ubap2l</i> leads to disorganized respiratory epithelium of mutant neonates, which die of respiratory failure. We also show that <i>UBAP2L</i> overexpression leads to epithelial-mesenchymal transition-like phenotype in a non-small cell lung carcinoma (NSCLC) cell line. <i>UBAP2L</i> is amplified in 15% of human primary lung adenocarcinoma specimens. Such patients express higher levels of <i>UBAP2L</i> and show a reduction in survival when compared with those who do not have this gene amplification. Supporting a possible role for <i>UBAP2L</i> in lung tumor progression, NSCLC cells engineered to express low levels of this gene produce much smaller tumors <i>in vivo</i> than wild-type control cells. Together, these results suggest that <i>UBAP2L</i> contributes to epithelial lung cell identity in mice and that it plays an important role in human lung adenocarcinoma.-Aucagne, R., Girard, S., Mayotte, N., Lehnertz, B., Lopes-Paciencia, S., Gendron, P., Boucher, G., Chagraoui, J., Sauvageau, G. <i>UBAP2L</i> is amplified in a large subset of human lung adenocarcinoma and is critical for epithelial lung cell identity and tumor metastasis.