{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:25:49Z","timestamp":1792095949447,"version":"4.4.0"},"reference-count":65,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":338,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["CA276863"],"award-info":[{"award-number":["CA276863"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["CA2211780"],"award-info":[{"award-number":["CA2211780"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["CA275327"],"award-info":[{"award-number":["CA275327"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,15]]},"abstract":"<jats:p>\n                    The high rate of recurrence after radiation therapy in triple-negative breast cancer (TNBC) indicates that novel approaches and targets are needed to enhance radiosensitivity. Here, we report that neuropilin-2 (\n                    <jats:italic>NRP2<\/jats:italic>\n                    ), a receptor for vascular endothelial growth factor (\n                    <jats:italic>VEGF<\/jats:italic>\n                    ) that is enriched on subpopulations of TNBC cells with stem cell properties, is an effective therapeutic target for sensitizing TNBC to radiotherapy. Specifically, VEGF\/NRP2 signaling induces nitric oxide synthase 2 (\n                    <jats:italic>NOS2<\/jats:italic>\n                    ) transcription by a mechanism dependent on Gli1. NRP2-expressing tumor cells serve as a hub to produce nitric oxide (NO), an autocrine and paracrine signaling metabolite, which promotes cysteine-nitrosylation of Kelch-like ECH-associated protein 1 (\n                    <jats:italic>KEAP1<\/jats:italic>\n                    ) and, consequently, nuclear factor erythroid 2-related factor 2\u2013mediated (\n                    <jats:italic>NFE2L2<\/jats:italic>\n                    -mediated) transcription of antioxidant response genes. Inhibiting VEGF binding to NRP2, using a humanized mAb, results in NFE2L2 degradation via KEAP1, rendering cell lines and organoids vulnerable to irradiation. Importantly, treatment of patient-derived xenografts with the NRP2 mAb and radiation resulted in significant tumor necrosis and regression compared with radiation alone. Together, these findings reveal a targetable mechanism of radioresistance, and they support the use of NRP2 mAb as an effective radiosensitizer in TNBC.\n                  <\/jats:p>","DOI":"10.1172\/jci181368","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T12:00:38Z","timestamp":1727784038000},"source":"Crossref","is-referenced-by-count":17,"title":["Neuropilin-2\u2013expressing breast cancer cells mitigate radiation-induced oxidative stress through nitric oxide signaling"],"prefix":"10.1172","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2816-8345","authenticated-orcid":true,"given":"Ayush","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Molecular, Cell and Cancer Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hira Lal","family":"Goel","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Cancer 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