{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T15:51:26Z","timestamp":1789314686339,"version":"build-2803163510"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"21","license":[{"start":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T00:00:00Z","timestamp":1684108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Translational Research Partnership","award":["KC200096P1"],"award-info":[{"award-number":["KC200096P1"]}]},{"DOI":"10.13039\/100007316","name":"Division of Cancer Prevention, National Cancer Institute","doi-asserted-by":"publisher","award":["NCI P30CA016672"],"award-info":[{"award-number":["NCI P30CA016672"]}],"id":[{"id":"10.13039\/100007316","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,5,23]]},"abstract":"<jats:p>\n                    Renal medullary carcinoma (RMC) is an aggressive kidney cancer that almost exclusively develops in individuals with sickle cell trait (SCT) and is always characterized by loss of the tumor suppressor\n                    <jats:italic>SMARCB1<\/jats:italic>\n                    . Because renal ischemia induced by red blood cell sickling exacerbates chronic renal medullary hypoxia in\u00a0vivo, we investigated whether the loss of SMARCB1 confers a survival advantage under the setting of SCT. Hypoxic stress, which naturally occurs within the renal medulla, is elevated under the setting of SCT. Our findings showed that hypoxia-induced SMARCB1 degradation protected renal cells from hypoxic stress. SMARCB1 wild-type renal tumors exhibited lower levels of SMARCB1 and more aggressive growth in mice harboring the SCT mutation in human hemoglobin A (HbA) than in control mice harboring wild-type human HbA. Consistent with established clinical observations, SMARCB1-null renal tumors were refractory to hypoxia-inducing therapeutic inhibition of angiogenesis. Further, reconstitution of SMARCB1 restored renal tumor sensitivity to hypoxic stress in\u00a0vitro and in\u00a0vivo. Together, our results demonstrate a physiological role for SMARCB1 degradation in response to hypoxic stress, connect the renal medullary hypoxia induced by SCT with an increased risk of SMARCB1-negative RMC, and shed light into the mechanisms mediating the resistance of SMARCB1-null renal tumors against angiogenesis inhibition therapies.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2209639120","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T15:15:35Z","timestamp":1684163735000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":27,"title":["SMARCB1 regulates the hypoxic stress response in sickle cell trait"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6902-898X","authenticated-orcid":false,"given":"Melinda","family":"Soeung","sequence":"first","affiliation":[{"name":"Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77025"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Perelli","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77025"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6916-5418","authenticated-orcid":false,"given":"Eleonora","family":"Dondossola","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025"},{"name":"David H. 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