{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:24:15Z","timestamp":1790198655216,"version":"4.1.0"},"reference-count":64,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III-FEDER","award":["PI21\/01378"],"award-info":[{"award-number":["PI21\/01378"]}]},{"name":"Instituto de Salud Carlos III-FEDER","award":["PI-067\/2013"],"award-info":[{"award-number":["PI-067\/2013"]}]},{"name":"Instituto de Salud Carlos III-FEDER","award":["C-0033-2015"],"award-info":[{"award-number":["C-0033-2015"]}]},{"name":"Instituto de Salud Carlos III-FEDER","award":["FI23\/00234"],"award-info":[{"award-number":["FI23\/00234"]}]},{"name":"Consejer\u00eda de Salud from the Junta de Andaluc\u00eda","award":["PI21\/01378"],"award-info":[{"award-number":["PI21\/01378"]}]},{"name":"Consejer\u00eda de Salud from the Junta de Andaluc\u00eda","award":["PI-067\/2013"],"award-info":[{"award-number":["PI-067\/2013"]}]},{"name":"Consejer\u00eda de Salud from the Junta de Andaluc\u00eda","award":["C-0033-2015"],"award-info":[{"award-number":["C-0033-2015"]}]},{"name":"Consejer\u00eda de Salud from the Junta de Andaluc\u00eda","award":["FI23\/00234"],"award-info":[{"award-number":["FI23\/00234"]}]},{"name":"Andalusian Health Service","award":["PI21\/01378"],"award-info":[{"award-number":["PI21\/01378"]}]},{"name":"Andalusian Health Service","award":["PI-067\/2013"],"award-info":[{"award-number":["PI-067\/2013"]}]},{"name":"Andalusian Health Service","award":["C-0033-2015"],"award-info":[{"award-number":["C-0033-2015"]}]},{"name":"Andalusian Health Service","award":["FI23\/00234"],"award-info":[{"award-number":["FI23\/00234"]}]},{"name":"Instituto de Salud Carlos III (Spain)","award":["PI21\/01378"],"award-info":[{"award-number":["PI21\/01378"]}]},{"name":"Instituto de Salud Carlos III (Spain)","award":["PI-067\/2013"],"award-info":[{"award-number":["PI-067\/2013"]}]},{"name":"Instituto de Salud Carlos III (Spain)","award":["C-0033-2015"],"award-info":[{"award-number":["C-0033-2015"]}]},{"name":"Instituto de Salud Carlos III (Spain)","award":["FI23\/00234"],"award-info":[{"award-number":["FI23\/00234"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>PARP-1 has been linked to the progression of several types of cancer. We have recently reported that PARP-1 influences tumor progression in CRC through the regulation of CSCs in a p53-dependent manner. In this study, we propose that nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) could act as a mediator. We evaluated the expression of iNOS in a cohort of patients previously used to analyze the effects of PARP-1 on CRC in relation to p53 status. We also developed an in vitro model in which PARP-1 was stably overexpressed. In CRC patients, iNOS expression correlated with the differentiation grade, and with a high expression of CSC markers, although only in wild-type p53 tumors, as previously found for PARP-1. In vitro, overexpression of PARP-1 induced increased growth and stemness in wild-type p53 cells, while exerting the opposite effect on mutated ones, as expected. Treatment with 1400 W, a selective inhibitor of iNOS, or gene silencing of the gene counteracted the effects of PARP-1 in both p53 wild-type and p53 mutated cells. Given that the development of resistance has been demonstrated after treatment with PARP-1 inhibitors, iNOS could be considered a new therapeutic target in CRC, although only in patients with wild-type p53 tumors.<\/jats:p>","DOI":"10.3390\/biom15010125","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T11:28:31Z","timestamp":1736854111000},"page":"125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["iNOS-Produced Nitric Oxide from Cancer Cells as an Intermediate of Stemness Regulation by PARP-1 in Colorectal Cancer"],"prefix":"10.3390","volume":"15","author":[{"given":"Mar\u00eda","family":"del Moral-Martinez","sequence":"first","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Aparato Digestivo, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"S\u00e1nchez-Uceta","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben","family":"Clemente-Gonzalez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Moreno-SanJuan","sequence":"additional","affiliation":[{"name":"Servicio de Microscop\u00eda y Citometr\u00eda, Instituto de Investigaci\u00f3n Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6417-6019","authenticated-orcid":false,"given":"Jose 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