Liu, Yu2019-11-08August 2012019-08August 201https://hdl.handle.net/10657/5331Lung cancer is the leading cause of cancer-related deaths in the United States, with KRAS and EGFR known as driver oncogenes for the disease. Adding to these are “lineage-survival oncogenes” where tumor survival depends on the aberrant expression of master transcriptional regulators of cell-lineages. Here, by integrating various patient gene expression datasets, we identified that basic helix- loop-helix transcription factor MESP1, a master regulator of mesendoderm development, has a previously-unknown association with Non-Small Cell Lung Cancer (NSCLC). We found that MESP1 expression correlates with poor prognosis in NSCLC patients, and is critical for proliferation and survival of NSCLC-derived cell lines, thus, implicating MESP1 as a lung cancer oncogene. Ectopic MESP1 expression cooperates with the loss of tumor suppressor ARF to transform murine fibroblasts. Xenografts of MESP1-knockdown cells showed decreased tumor growth in vivo. Global transcriptome analysis revealed a MESP1 DNA-binding dependent gene signature associated with various hallmarks of cancer, suggesting that the transcription activity of MESP1 is most likely responsible for its oncogenic abilities. These observations demonstrate MESP1 as a previously-unknown lineage survival oncogene in NSCLC.application/pdfengThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).MESP1Lung cancerARFEMT2019-11-08Thesisborn digital