{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T14:50:52Z","timestamp":1785336652613,"version":"3.55.0"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"NIH","award":["ZIA BC 011255"],"award-info":[{"award-number":["ZIA BC 011255"]}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Patients with ER-negative breast cancer have the worst prognosis of all breast cancer subtypes, often experiencing rapid recurrence or progression to metastatic disease shortly after diagnosis. Given that metastasis is the primary cause of mortality in most solid tumors, understanding metastatic biology is crucial for effective intervention. Using a mouse systems genetics approach, we previously identified 12 genes associated with metastatic susceptibility. Here, we extend those studies to identify <jats:italic>Resf1<\/jats:italic>, a poorly characterized gene, as a novel metastasis susceptibility gene in ER- breast cancer. <jats:italic>Resf1<\/jats:italic> is a large, unstructured protein with an evolutionarily conserved intron-exon structure, but with poor amino acid conservation. CRISPR or gene trap mouse models crossed to the Polyoma Middle-T antigen genetically engineered mouse model (MMTV-PyMT) demonstrated that reduction of <jats:italic>Resf1<\/jats:italic> resulted in a significant increase in tumor growth, a shortened overall survival time, and increased incidence and number of lung metastases, consistent with patient data. Furthermore, an analysis of matched tail and primary tissues revealed loss of the wildtype copy in tumor tissue, consistent with <jats:italic>Resf1<\/jats:italic> being a tumor suppressor. Mechanistic analysis revealed a potential role of <jats:italic>Resf1<\/jats:italic> in transcriptional control through association with compound G4 quadruplexes in expressed sequences, particularly those associated with ribosomal biogenesis. These results suggest that loss of <jats:italic>Resf1<\/jats:italic> enhances tumor progression in ER- breast cancer through multiple alterations in both transcriptional and translational control.<\/jats:p>","DOI":"10.1371\/journal.pgen.1011236","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T17:21:53Z","timestamp":1715275313000},"page":"e1011236","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Resf1 is a compound G4 quadruplex-associated tumor suppressor for triple negative breast cancer"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7378-7408","authenticated-orcid":true,"given":"Megan R.","family":"Majocha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin E.","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngoc-Han","family":"Ha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8826-4040","authenticated-orcid":true,"given":"Ruhul","family":"Amin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4184-4296","authenticated-orcid":true,"given":"Marie","family":"Pangr\u00e1cov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina R.","family":"Ross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9291-631X","authenticated-orcid":true,"given":"Howard H.","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3738-1292","authenticated-orcid":true,"given":"Maxwell P.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5963-8808","authenticated-orcid":true,"given":"Kent W.","family":"Hunter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"pgen.1011236.ref001","unstructured":"SEER [Internet]. 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