{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:30:42Z","timestamp":1790094642337,"version":"4.0.1"},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T00:00:00Z","timestamp":1672272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81974533"],"award-info":[{"award-number":["81974533"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:p>\n                    Mild hypothermia can induce apoptotic cell death in many cancer cells, but the underlying mechanisms remain unclear. In a genetic screen in\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    , we found that impaired endoplasmic reticulum unfolded protein response (UPR\n                    <jats:sup>ER<\/jats:sup>\n                    ) increased animal survival after cold shock. Consistently, in normal human lung cells, decreasing culture temperature from 37 to 30\u2009\u00b0C activated UPR\n                    <jats:sup>ER<\/jats:sup>\n                    and promoted cell death. However, lung adenocarcinoma cells were impaired in UPR\n                    <jats:sup>ER<\/jats:sup>\n                    induction and resistant to hypothermia\u2010induced cell death. Mechanistically, hypothermic stress increased HSF1 levels, which in turn activated UPR\n                    <jats:sup>ER<\/jats:sup>\n                    to promote apoptotic cell death. HSF1 expression was associated with UPR\n                    <jats:sup>ER<\/jats:sup>\n                    genes in normal tissues, but such association was lost in many cancers, especially lung adenocarcinoma. Activating UPR\n                    <jats:sup>ER<\/jats:sup>\n                    enhanced the cytotoxicity of chemotherapy drugs cisplatin preferentially in cancer cells. Consistently, cancer patients with higher UPR\n                    <jats:sup>ER<\/jats:sup>\n                    expression had generally better prognosis. Together, our study on hypothermia has led to the discovery of HSF1\u2010UPR\n                    <jats:sup>ER<\/jats:sup>\n                    in the regulation of drug sensitivity in lung cancer cells, providing novel thoughts on developing new strategies against chemoresistance.\n                  <\/jats:p>","DOI":"10.1111\/febs.16709","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T01:53:49Z","timestamp":1671501229000},"page":"2706-2720","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Deregulation of\n                    <scp>HSF1<\/scp>\n                    \u2010mediated endoplasmic reticulum unfolded protein response promotes cisplatin resistance in lung cancer cells"],"prefix":"10.1111","volume":"290","author":[{"given":"Min","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, the Second Xiangya Hospital Central South University  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