{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:05:29Z","timestamp":1790388329619,"version":"4.1.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T00:00:00Z","timestamp":1581465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP15K11252"],"award-info":[{"award-number":["JP15K11252"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We previously demonstrated that expression of a Kr\u00fcppel-like zinc finger transcription factor, GLIS1, dramatically increases under hypoxic conditions via a transcriptional mechanism induced by HIF-2\u03b1 cooperating with AP-1 members. In this study, we focused on the functional roles of GLIS1 in breast cancer. To uncover its biological function, the effects of altered levels of GLIS1 in breast cancer cell lines on cellular growth, wound-healing and invasion capacities were assessed. Knockdown of GLIS1 using siRNA in BT-474 cells resulted in significant growth stimulation under normoxia, while attenuation was found in the cell invasion assay under hypoxic conditions. In MDA-MB-231 cells expressing exogenous 3xFLAG-tagged GLIS1, GLIS1 attenuated cell proliferation and enhanced cell mobility and invasion capacities under normoxia. In addition, breast cancer cells expressing GLIS1 acquired resistance to irradiation. Whole transcriptome analysis clearly demonstrated that downstream signals of GLIS1 are related to various cellular functions. Among the genes with increased expression, we focused on WNT5A. Knockdown of WNT5A indicated that enhancement of acquired cell motility in the MDA-MB-231 cells expressing GLIS1 was mediated, at least in part, by WNT5A. In an analysis of publicly available data, patients with estrogen receptor-negative breast cancer showing high levels of GLIS1 expression showed much worse prognosis than those with low levels. In summary, hypoxia-induced GLIS1 plays significant roles in breast cancer cells via regulation of gene expression related to cell migration and invasion capacities, resulting in poorer prognosis in patients with advanced breast cancer.<\/jats:p>","DOI":"10.1093\/carcin\/bgaa010","type":"journal-article","created":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T12:08:18Z","timestamp":1581077298000},"page":"1184-1194","source":"Crossref","is-referenced-by-count":16,"title":["GLIS1, a novel hypoxia-inducible transcription factor, promotes breast cancer cell motility via activation of WNT5A"],"prefix":"10.1093","volume":"41","author":[{"given":"Kazumi","family":"Shimamoto","sequence":"first","affiliation":[{"name":"Department of Radiation Disaster Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4912-4197","authenticated-orcid":false,"given":"Keiji","family":"Tanimoto","sequence":"additional","affiliation":[{"name":"Department of Radiation Disaster Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Fukazawa","sequence":"additional","affiliation":[{"name":"Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine, Saga University Hospital, Saga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinori","family":"Kanai","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4413-0651","authenticated-orcid":false,"given":"Hidemasa","family":"Bono","sequence":"additional","affiliation":[{"name":"Database Center for Life Science, Joint Support-Center for Data Science Research, Research Organization of Information and Systems, Mishima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromasa","family":"Ono","sequence":"additional","affiliation":[{"name":"Database Center for Life Science, Joint Support-Center for Data Science Research, Research Organization of Information and Systems, Mishima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetaka","family":"Eguchi","sequence":"additional","affiliation":[{"name":"Diagnosis and Therapeutics of Intractable Diseases and Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Hirohashi","sequence":"additional","affiliation":[{"name":"Department of Radiation Disaster Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,2,12]]},"reference":[{"key":"2020092413443829300_CIT0001","doi-asserted-by":"crossref","first-page":"30901","DOI":"10.1074\/jbc.M203563200","article-title":"Identification of Glis1, a novel Gli-related, Kruppel-like zinc finger protein containing transactivation and repressor functions","volume":"277","author":"Kim","year":"2002","journal-title":"J. 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