{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T04:29:31Z","timestamp":1773462571274,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T00:00:00Z","timestamp":1677542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"WVCTSI-NIH-NIGMS","award":["U54 GM104942"],"award-info":[{"award-number":["U54 GM104942"]}]},{"name":"WVCTSI-NIH-NIGMS","award":["IRG-09-061-04"],"award-info":[{"award-number":["IRG-09-061-04"]}]},{"name":"ACS","award":["U54 GM104942"],"award-info":[{"award-number":["U54 GM104942"]}]},{"name":"ACS","award":["IRG-09-061-04"],"award-info":[{"award-number":["IRG-09-061-04"]}]},{"name":"publication was supported by Carol Ann and Ralph V. Haile, Jr Foundation awarded to Wood Hudson Cancer Research Laboratory","award":["U54 GM104942"],"award-info":[{"award-number":["U54 GM104942"]}]},{"name":"publication was supported by Carol Ann and Ralph V. Haile, Jr Foundation awarded to Wood Hudson Cancer Research Laboratory","award":["IRG-09-061-04"],"award-info":[{"award-number":["IRG-09-061-04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Identifying cellular drivers responsible for enhancing cancer cell resistance to therapeutics provides critical information for designing more effective drugs. Populations of slowly growing, self-renewing, chemo-resistant cells purportedly contribute to the development of therapeutic resistance in many solid tumors. In the current study, we implemented a tumor spheroid model to determine whether NAD(P)H quinone oxidoreductase-1 (NQO1) was requisite for self-renewal and promotion of the drug-resistant phenotype in non-small cell lung cancer (NSCLC). We found that stable depletion of NQO1 in A549 and H358 human NSCLC tumor models inhibits self-renewal capabilities, as demonstrated by a reduced ability to form primary, secondary, and tertiary spheroids. In contrast, the rescue of NQO1 expression restored the tumor cells\u2019 ability to form spheroids. Additionally, we discovered that NQO1 depletion renders cisplatin-refractory tumor spheroids highly susceptible to drug treatment. Together, these results suggest that NQO1 loss reduces the self-renewing capabilities of NSCLC cells and enhances their susceptibility to clinically relevant therapeutics. These findings describe a novel role for NQO1 and suggest that combining NQO1-inhibitors with conventional chemotherapeutics may enhance anti-tumor effects.<\/jats:p>","DOI":"10.3390\/genes14030607","type":"journal-article","created":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T03:29:46Z","timestamp":1677554986000},"page":"607","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["NAD(P)H Quinone Oxidoreductase-1 Expression Promotes Self-Renewal and Therapeutic Resistance in Non-Small Cell Lung Cancer"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6156-0405","authenticated-orcid":false,"given":"Brian","family":"Madajewski","sequence":"first","affiliation":[{"name":"Memorial Sloan Kettering-Cornell Center for Translation of Cancer Nanomedicine, Memorial Sloan Kettering Cancer Center, 415 East 68th Street, New York, NY 10065, USA"},{"name":"West Virginia University Cancer Institute, West Virginia University, 1 Medical Center Drive, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Boatman","sequence":"additional","affiliation":[{"name":"West Virginia University Cancer Institute, West Virginia University, 1 Medical Center Drive, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Martinez","sequence":"additional","affiliation":[{"name":"West Virginia University Cancer Institute, West Virginia University, 1 Medical Center Drive, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia H.","family":"Carter","sequence":"additional","affiliation":[{"name":"Wood Hudson Cancer Research Laboratory Inc., 931 Isabella Street, Newport, KY 41701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik A.","family":"Bey","sequence":"additional","affiliation":[{"name":"West Virginia University Cancer Institute, West Virginia University, 1 Medical Center Drive, Morgantown, WV 26506, USA"},{"name":"Wood Hudson Cancer Research Laboratory Inc., 931 Isabella Street, Newport, KY 41701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1002\/cncr.28509","article-title":"Annual Report to the Nation on the status of cancer, 1975\u20132010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer","volume":"120","author":"Edwards","year":"2014","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer statistics, 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"CA Cancer J. 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