{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:58:51Z","timestamp":1790305131457,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020051","name":"Tamura Science and Technology Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hyperthermia, induced by heat stress (HS), inhibits cancer cell proliferation and induces cell death. We have previously demonstrated that the inhibition of checkpoint kinase 1\/2 (Chk1\/2) abrogated G2\/M arrest and promoted cell death under HS conditions. Here, we investigated whether Wee1 inhibition promoted mitotic entry and cell death in cells exposed to HS in combination with a Chk1\/2 inhibitor. MK\u20101775, a selective Wee1 inhibitor, promoted HS\u2010induced loss of cell viability and increased the SubG1 population in HeLa S3 cells, accompanied by enhanced recovery of EdU incorporation and reduced G2\u2010phase accumulation following HS. Either MK\u20101775 or AZD\u20107762, a Chk1\/2 inhibitor, alone counteracted HS\u2010induced suppression of EdU incorporation and G2 arrest, whereas their combination further promoted EdU incorporation, mitotic entry, and loss of cell viability under HS. These findings suggest that Wee1 and Chk1\/2 cooperatively regulate both S\u2010phase progression and mitotic entry under HS, thereby contributing to cell survival. Moreover, the combination of MK\u20101775 and AZD\u20107762 abrogated G2 arrest and enhanced HS\u2010induced cell death in MG\u201063 and HSC\u20103 cells. These findings indicate that simultaneous inhibition of Wee1 and Chk1\/2 could be a promising strategy for augmenting the therapeutic efficacy of hyperthermia.<\/jats:p>","DOI":"10.1111\/gtc.70140","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:27:26Z","timestamp":1785320846000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined Inhibition of Wee1 and Checkpoint Kinases Synergistically Provokes S\u2010Phase Progression and Mitotic Entry, and Promotes Cell Death Under Heat Stress"],"prefix":"10.1111","volume":"31","author":[{"given":"Tamaki","family":"Muratani","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Engineering, Faculty of Engineering Toyama Prefectural University  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honoka","family":"Takeya","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, Faculty of Engineering Toyama Prefectural University  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riko","family":"Ishibashi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, Faculty of Engineering Toyama Prefectural University  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuto","family":"Kurakawa","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Engineering Toyama Prefectural University  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5311-4069","authenticated-orcid":false,"given":"Shin\u2010ichi","family":"Ikushiro","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Engineering Toyama Prefectural University  Toyama 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