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Notably, Rumi is a \u201cprotein <jats:italic>O<\/jats:italic>\u2010glucosyltransferase\u201d that regulates Notch signaling through <jats:italic>O<\/jats:italic>\u2010glucosylation of Notch receptors, and is the only enzymatic regulator whose activity is required for both ligand\u2010dependent and ligand\u2010independent activation of Notch. We have conducted a detailed study on RUMI\u2019s involvement in NSCLC development and progression, and have further explored the therapeutic potential of its targeting in NSCLC. We have determined that Rumi is highly expressed in the alveolar and bronchiolar epithelia, including club cells and alveolar type II cells. Remarkably, <jats:italic>RUMI<\/jats:italic> maps to the region of chromosome 3q that corresponds to the major signature of neoplastic transformation in NSCLC, and is markedly amplified and overexpressed in NSCLC tumors. Notably, RUMI expression levels are predictive of poor prognosis and survival in NSCLC patients. Our data indicates that RUMI modulates Notch activity in NSCLC cells, and that its silencing dramatically decreases cell proliferation, migration, and survival. RUMI downregulation causes severe cell cycle S\u2010phase arrest, increases genome instability, and induces late apoptotic\u2013nonapoptotic cell death. Our studies demonstrate that RUMI is a novel negative prognostic factor with significant therapeutic potential in NSCLC, which embodies particular relevance especially when considering that, while current Notch inhibitory strategies target only ligand\u2010dependent Notch activation, a large number of NSCLCs are driven by ligand\u2010independent Notch activity.<\/jats:p>","DOI":"10.1002\/jcp.26858","type":"journal-article","created":{"date-parts":[[2018,6,28]],"date-time":"2018-06-28T20:16:22Z","timestamp":1530216982000},"page":"9548-9562","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["RUMI is a novel negative prognostic marker and therapeutic target in non\u2013small\u2010cell lung cancer"],"prefix":"10.1002","volume":"233","author":[{"given":"May","family":"Chammaa","sequence":"first","affiliation":[{"name":"Department of Pathology Wayne State University School of Medicine  Detroit Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnes","family":"Malysa","sequence":"additional","affiliation":[{"name":"Department of Oncology Wayne State University School of Medicine  Detroit Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Redondo","sequence":"additional","affiliation":[{"name":"Department of Pathology Wayne State University School of Medicine  Detroit Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyejeong","family":"Jang","sequence":"additional","affiliation":[{"name":"Biostatistics Core Barbara Ann Karmanos Cancer Institute  Detroit Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oncology Wayne State University School of Medicine  Detroit Michigan"},{"name":"Biostatistics Core Barbara Ann Karmanos Cancer Institute  Detroit Michigan"},{"name":"Cancer Biology Graduate Program Wayne State University School of Medicine  Detroit Michigan"},{"name":"Tumor Biology and Microenvironment Program Barbara Ann Karmanos Cancer Institute  Detroit Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerold","family":"Bepler","sequence":"additional","affiliation":[{"name":"Department of Oncology Wayne State University School of Medicine  Detroit Michigan"},{"name":"Cancer Biology Graduate Program Wayne State University School of Medicine  Detroit Michigan"},{"name":"Molecular Therapeutics Program Barbara Ann Karmanos Cancer Institute  Detroit Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6873-5706","authenticated-orcid":false,"given":"Rodrigo","family":"Fernandez\u2010Valdivia","sequence":"additional","affiliation":[{"name":"Department of Pathology Wayne State University School of Medicine  Detroit Michigan"},{"name":"Department of Oncology Wayne State University School of Medicine  Detroit Michigan"},{"name":"Cancer Biology Graduate Program Wayne State University School of Medicine  Detroit Michigan"},{"name":"Tumor Biology and Microenvironment Program Barbara Ann Karmanos Cancer Institute  Detroit Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,6,28]]},"reference":[{"key":"e_1_2_7_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.12.016"},{"key":"e_1_2_7_1_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-0595"},{"issue":"3","key":"e_1_2_7_1_4_1","first-page":"270","article-title":"Combined inhibition of DDR1 and Notch signaling is a therapeutic strategy for KRAS\u2010driven lung adenocarcinoma","volume":"22","author":"Ambrogio C.","year":"2016","journal-title":"Nature Medicine (New York, NY, United States)"},{"issue":"11","key":"e_1_2_7_1_5_1","first-page":"2116","article-title":"Comparative genomic hybridization analysis detects frequent, often high\u2010level, overrepresentation of DNA sequences at 3q, 5p, 7p, and 8q in human non\u2010small cell lung carcinomas","volume":"57","author":"Balsara B. 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