{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T16:24:15Z","timestamp":1783700655422,"version":"3.55.0"},"reference-count":52,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T00:00:00Z","timestamp":1603843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH1010386"],"award-info":[{"award-number":["W81XWH1010386"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>High-grade serous carcinoma (HGSC), the most lethal subtype of epithelial ovarian cancer (EOC), is characterized by widespread TP53 mutations (&gt;90%), most of which are missense mutations (&gt;70%). The objective of this study was to investigate differential transcriptional targets affected by a common germline P72R SNP (rs1042522) in two p53 hotspot mutants, R248Q and R248W, and identify the mechanism through which the P72R SNP affects the neomorphic properties of these mutants. Using isogenic cell line models, transcriptomic analysis, xenografts, and patient data, we found that the P72R SNP modifies the effect of p53 hotspot mutants on cellular morphology and invasion properties. Most importantly, RNA sequencing studies identified CXCL1 a critical factor that is differentially affected by P72R SNP in R248Q and R248W mutants and is responsible for differences in cellular morphology and functional properties observed in these p53 mutants. We show that the mutants with the P72 SNP promote a reversion of the EMT phenotype to epithelial characteristics, whereas its R72 counterpart promotes a mesenchymal transition via the chemokine CXCL1. These studies reveal a new role of the P72R SNP in modulating the neomorphic properties of p53 mutants via CXCL1, which has significant implications for tumor invasion and metastasis.<\/jats:p>","DOI":"10.3390\/ijms21218025","type":"journal-article","created":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T11:43:06Z","timestamp":1603885386000},"page":"8025","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The P72R Polymorphism in R248Q\/W p53 Mutants Modifies the Mutant Effect on Epithelial to Mesenchymal Transition Phenotype and Cell Invasion via CXCL1 Expression"],"prefix":"10.3390","volume":"21","author":[{"given":"Cristabelle","family":"De Souza","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, University of California Davis Medical Center, Sacramento, CA 95817, USA"},{"name":"University of New Mexico School of Medicine, Biomedical Sciences Graduate Program, Albuquerque, NM 87106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill A.","family":"Madden","sequence":"additional","affiliation":[{"name":"The Manton Center for Orphan Disease Research and The Division of Genetics and Genomics, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Minn","sequence":"additional","affiliation":[{"name":"College of Information and Computer Sciences, University of Massachusetts, Amherst, MA 01003, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vigneshwari Easwar","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, University of California Davis Medical Center, Sacramento, CA 95817, USA"},{"name":"Department of Biology, California State University, Channel Islands, CA 93012, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis J.","family":"Montoya","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, University of California Davis Medical Center, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshni","family":"Nambiar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, University of California Davis Medical Center, Sacramento, CA 95817, USA"},{"name":"Department of Biology, California State University, Channel Islands, CA 93012, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4112-5294","authenticated-orcid":false,"given":"Zheng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, University of California Davis Medical Center, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Wu","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, University of California Davis Medical Center, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeki","family":"Tahmassebi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, University of California Davis Medical Center, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7242-8127","authenticated-orcid":false,"given":"Harikumara","family":"Kathi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, University of California Davis Medical Center, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, University of California Davis Medical Center, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony N.","family":"Karnezis","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, UC Davis Medical Center, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4744-8374","authenticated-orcid":false,"given":"Jeremy","family":"Chien","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, University of California Davis Medical Center, Sacramento, CA 95817, USA"},{"name":"Department of Obstetrics and Gynecology, University of California Davis Medical Center, Sacramento, CA 95817, 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