{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:10:32Z","timestamp":1789452632299,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T00:00:00Z","timestamp":1593475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP17K08697"],"award-info":[{"award-number":["JP17K08697"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP17K08698"],"award-info":[{"award-number":["JP17K08698"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP18K15084"],"award-info":[{"award-number":["JP18K15084"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19K16561"],"award-info":[{"award-number":["JP19K16561"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Recent studies have revealed that metabolic reprogramming is closely associated with epithelial\u2010mesenchymal transition (EMT) during cancer progression. Aldolase A (ALDOA) is a key glycolytic enzyme that is highly expressed in several types of cancer. In this study, we found that ALDOA is highly expressed in uterine cervical adenocarcinoma and that high ALDOA expression promotes EMT to increase malignant potentials, such as metastasis and invasiveness, in cervical adenocarcinoma cells. In human surgical specimens, ALDOA was highly expressed in cervical adenocarcinoma and high ALDOA expression was correlated with lymph node metastasis, lymphovascular infiltration, and short overall survival. Suppression of ALDOA expression significantly reduced cell growth, migration, and invasiveness of cervical cancer cells. Aldolase A expression was partially regulated by hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1). Shotgun proteome analysis revealed that cell\u2010cell adhesion\u2010related proteins were significantly increased in ALDOA\u2010overexpressing cells. Interestingly, overexpression of ALDOA caused severe morphological changes, including a cuboidal\u2010to\u2010spindle shape shift and reduced microvilli formation, coincident with modulation of the expression of typical EMT\u2010related proteins. Overexpression of ALDOA increased migration and invasion in vitro. Furthermore, overexpression of ALDOA induced HIF\u20101\u03b1, suggesting a positive feedback loop between ALDOA and HIF\u20101\u03b1. In conclusion, ALDOA is overexpressed in cervical adenocarcinoma and contributes to malignant potentials of tumor cells through modulation of HIF\u20101\u03b1 signaling. The feedback loop between ALDOA and HIF\u20101\u03b1 could become a therapeutic target to improve the prognosis of this malignancy.<\/jats:p>","DOI":"10.1111\/cas.14524","type":"journal-article","created":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T09:18:17Z","timestamp":1591953497000},"page":"3071-3081","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Aldolase A promotes epithelial\u2010mesenchymal transition to increase malignant potentials of cervical adenocarcinoma"],"prefix":"10.1111","volume":"111","author":[{"given":"Yuki","family":"Saito","sequence":"first","affiliation":[{"name":"Department of Pathology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3244-1199","authenticated-orcid":false,"given":"Akira","family":"Takasawa","sequence":"additional","affiliation":[{"name":"Department of Pathology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumi","family":"Takasawa","sequence":"additional","affiliation":[{"name":"Department of Pathology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Aoyama","sequence":"additional","affiliation":[{"name":"Department of Pathology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taishi","family":"Akimoto","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misaki","family":"Ota","sequence":"additional","affiliation":[{"name":"Department of Pathology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazufumi","family":"Magara","sequence":"additional","affiliation":[{"name":"Department of Pathology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Murata","sequence":"additional","affiliation":[{"name":"Department of Pathology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0608-3914","authenticated-orcid":false,"given":"Yoshihiko","family":"Hirohashi","sequence":"additional","affiliation":[{"name":"Department of Pathology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norimasa","family":"Sawada","sequence":"additional","affiliation":[{"name":"Department of Pathology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1754-252X","authenticated-orcid":false,"given":"Makoto","family":"Osanai","sequence":"additional","affiliation":[{"name":"Department of Pathology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-05-0231"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20678"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2009.09.040"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)04646-8"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.2000.5826"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19980209)75:4<536::AID-IJC8>3.0.CO;2-U"},{"key":"e_1_2_7_8_1","first-page":"18157","article-title":"Elevated expression of G protein\u2010coupled receptor 30 (GPR30) is associated with poor prognosis in patients with uterine cervical adenocarcinoma","volume":"35","author":"Ino Y","year":"2020","journal-title":"Histol Histopathol"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0144887"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2012.06.021"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.2000.5935"},{"key":"e_1_2_7_12_1","first-page":"325","volume-title":"Blaustein\u2019s Pathology of The Female Genital Tract","author":"Wright TC","year":"2002"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.3802\/jgo.2017.28.e19"},{"key":"e_1_2_7_14_1","first-page":"921","article-title":"Analysis of the expression and localization of tight junction transmembrane proteins, claudin\u20101, \u20104, \u20107, occludin and JAM\u2010A, in human cervical adenocarcinoma","volume":"31","author":"Akimoto T","year":"2016","journal-title":"Histol Histopathol"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2018.08.010"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.12012"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdq723"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)35789-7"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.1860080306"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085804"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M800422-MCP200"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr800197z"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-016-5275-8"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2014.3473"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.21957"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2016.01.054"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2018.05.003"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2016.3814"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13040-016-0122-4"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep33582"},{"key":"e_1_2_7_31_1","first-page":"603","article-title":"Establishment of a human adenocarcinoma cell line, CAC\u20101","volume":"57","author":"Hayakawa O","year":"1988","journal-title":"Sapporo Med J"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.1996.0033"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2019.01.013"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13385"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.05.033"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr700658q"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2012.244"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1778"},{"issue":"18","key":"e_1_2_7_39_1","doi-asserted-by":"crossref","first-page":"4754","DOI":"10.1158\/0008-5472.CAN-18-4080","article-title":"Therapeutic targeting of aldolase A interactions inhibits lung cancer metastasis and prolongs survival","volume":"79","author":"Chang Y\u2010C","year":"2019","journal-title":"Cancer Res"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.1132"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2005.09.018"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13732"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.02.123"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.188243"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.11.8.15274"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14090"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2016.302"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.215"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-015-0221-y"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-0401"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcas.14524","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.14524","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.14524","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.14524","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T09:35:07Z","timestamp":1693560907000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.14524"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,30]]},"references-count":49,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1111\/cas.14524"],"URL":"https:\/\/doi.org\/10.1111\/cas.14524","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,30]]},"assertion":[{"value":"2019-12-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}