{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:28:21Z","timestamp":1787005701023,"version":"build-2736575974"},"reference-count":22,"publisher":"National Academy of Sciences","issue":"39","license":[{"start":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T00:00:00Z","timestamp":1583452800000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,9,24]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>The clinical effectiveness of FDA-approved anticancer rapalogs is limited because resistance is observed in multiple-tumor settings. In order to improve the efficacy of rapalogs, there is a need to improve our ability to predict and overcome rapamycin resistance. Here we report that high FRAT1\/2 expression confers rapamycin resistance by excluding GSK3 from the nucleus in multiple-cancer cell lines. FRAT1 expression is frequently high in multiple cancers, and our observations provide evidence for using FRAT1\/2 expression as a biomarker for rapamycin sensitivity. Moreover, our findings reveal a major mechanism for how mTORC1 regulates nuclear protein phosphorylation and signaling, and uncover a potential therapeutic approach for targeting mTORC1-driven cancers.<\/jats:p>","DOI":"10.1073\/pnas.1902397116","type":"journal-article","created":{"date-parts":[[2019,9,6]],"date-time":"2019-09-06T20:45:28Z","timestamp":1567802728000},"page":"19523-19529","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":25,"title":["Regulation of GSK3 cellular location by FRAT modulates mTORC1-dependent cell growth and sensitivity to rapamycin"],"prefix":"10.1073","volume":"116","author":[{"given":"Long","family":"He","sequence":"first","affiliation":[{"name":"Meyer Cancer Center, Weill Cornell Medical College, New York, NY 10021;"},{"name":"Department of Pharmacology, Weill Cornell Medical College, New York, NY 10021;"},{"name":"World Class Institute, Korea Research Institute of Bioscience and Biotechnology, 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