{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T10:32:04Z","timestamp":1788690724777,"version":"build-2803163510"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T00:00:00Z","timestamp":1586995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2014R1A2A1A11053203"],"award-info":[{"award-number":["NRF-2014R1A2A1A11053203"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2017R1A2B2006839"],"award-info":[{"award-number":["NRF-2017R1A2B2006839"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2018R1A5A2025964"],"award-info":[{"award-number":["NRF-2018R1A5A2025964"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004332","name":"Seoul National University Hospital","doi-asserted-by":"publisher","award":["0320190210"],"award-info":[{"award-number":["0320190210"]}],"id":[{"id":"10.13039\/501100004332","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Circadian oscillation is an essential process that influences many physiological and biological mechanisms and a decrease of circadian genes is associated with many diseases such as cancer. Despite many efforts to identify the detailed mechanism for decreasing circadian genes and recovering reduced circadian genes in cancer, it is still largely unknown. We found that BMAL1 was reduced in tumor hypoxia-induced acidosis, and recovered by selectively targeting acidic pH in breast cancer cell lines. Surprisingly, BMAL1 was reduced by decrease of protein stability as well as inhibition of transcription under acidosis. In addition, melatonin significantly prevented acidosis-mediated decrease of BMAL1 by inhibiting lactate dehydrogenase-A during hypoxia. Remarkably, acidosis-mediated metastasis was significantly alleviated by BMAL1 overexpression in breast cancer cells. We therefore suggest that tumor hypoxia-induced acidosis promotes metastatic potency by decreasing BMAL1, and that tumor acidosis could be a target for preventing breast cancer metastasis by sustaining BMAL1.<\/jats:p>","DOI":"10.3390\/cells9040989","type":"journal-article","created":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T13:01:39Z","timestamp":1587042099000},"page":"989","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Extracellular Acidosis Promotes Metastatic Potency via Decrease of the BMAL1 Circadian Clock Gene in Breast Cancer"],"prefix":"10.3390","volume":"9","author":[{"given":"Yong-Jin","family":"Kwon","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Bi","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun-Ho","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song-Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seul-Ki","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Ki","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungjin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SaeGwang","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, INJE University College of Medicine, 633-165 GaegumDong, Busanjin Gu, Busan 614-735, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Chul","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Nowon-gu, Seoul 01812, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Wan","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Ischemic\/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Kyu","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Ischemic\/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Neuro-Immune Information Storage Network Research Center, Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21442","article-title":"Cancer statistics, 2018","volume":"68","author":"Siegel","year":"2018","journal-title":"CA Cancer J. 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