{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:33:58Z","timestamp":1788572038964,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2016 M600524"],"award-info":[{"award-number":["2016 M600524"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:p>Most common ovarian cancers are epithelial carcinoma in which the etiology for carcinogenesis remains elusive. ANO1\/TMEM16A, a member of Ca<jats:sup>2+<\/jats:sup>\u2010activated Cl<jats:sup>\u2212<\/jats:sup> channels (CaCCs), has been demonstrated to promote epithelium\u2010originated cancers and whether it plays a role in the pathogenesis of ovarian cancer is unknown. In our study we found that ANO1 proteins were overexpressed in human epithelial ovarian cancer cells and tissue samples. ANO1 protein upregulation was correlated with the clinical FIGO (International Federation of Gynecology and Obstetrics) staging and poor grade in ovarian cancer tissues. Interestingly, the upregulation of ANO1 gene expression was also detected in the peripheral blood mononuclear cells (PBMCs) from preoperative patients with ovarian tumors, and the down\u2010regulation of ANO1 in the PBMCs from postoperative patients. Silencing of ANO1 inhibited proliferation and invasion of ovarian cancer cells. Mechanistically, ANO1 knockdown attenuated phosphorylation of PI3K\/Akt, and inhibition of PI3K\/Akt signaling by specific inhibitor LY294002 resulted in suppression of ovarian cancer cells growth promoted by ANO1 expression. Furthermore, intratumoral injection of ANO1 siRNA suppressed subcutaneous xenograft tumor growth in nude mice implanted with ovarian cancer SKOV3 cells. Taken together, our findings demonstrate that ANO1 overexpression is involved in the pathogenesis of human epithelial ovarian cancer. Inhibition of ANO1 upregulation or inactivating PI3K\/Akt signaling may have therapeutic potential for epithelial ovarian cancer, and the detection of ANO1 expression level in PBMCs from patients may also serve as a biomarker for diagnosis and prognosis of epithelial ovarian cancers.<\/jats:p>","DOI":"10.1002\/ijc.31887","type":"journal-article","created":{"date-parts":[[2018,9,22]],"date-time":"2018-09-22T16:18:12Z","timestamp":1537633092000},"page":"2215-2226","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Inhibition of Ca<sup>2+<\/sup>\u2010activated chloride channel ANO1 suppresses ovarian cancer through inactivating PI3K\/Akt signaling"],"prefix":"10.1002","volume":"144","author":[{"given":"Zongtao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacology Qingdao University School of Pharmacy  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Qingdao University School of Pharmacy  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Clinicopathology Qingdao University Affiliated Hospital  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congxiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Qingdao University School of Pharmacy  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Qingdao University School of Pharmacy  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7023-9998","authenticated-orcid":false,"given":"KeWei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Qingdao University School of Pharmacy  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21254"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800306"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2014-0097"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2008.12.003"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3109\/08830185.2014.921161"},{"key":"e_1_2_7_7_1","first-page":"6077","article-title":"Volume\u2010sensitive chloride channels associated with human cervical carcinogenesis","volume":"55","author":"Chou CY","year":"1995","journal-title":"Cancer Res"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.67.032003.154341"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-002-0805-1"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.29"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1163518"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.09.003"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07313"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.26232"},{"key":"e_1_2_7_15_1","first-page":"1966","article-title":"Tissue microarrays for gene amplification surveys in many different tumor types","volume":"5","author":"Schraml P","year":"1999","journal-title":"Clin Cancer Res"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3277"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1217072110"},{"key":"e_1_2_7_18_1","first-page":"325","article-title":"Knockdown of TMEM16A suppressed MAPK and inhibited cell proliferation and migration in hepatocellular carcinoma","volume":"9","author":"Deng L","year":"2016","journal-title":"OncoTargets Ther"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0136584"},{"key":"e_1_2_7_20_1","doi-asserted-by":"crossref","first-page":"36645","DOI":"10.18632\/oncotarget.9128","article-title":"Circulating tumor cells as a prognostic and predictive marker in gastrointestinal stromal tumors: a prospective study","volume":"7","author":"Li Q","year":"2016","journal-title":"Oncotarget"},{"key":"e_1_2_7_21_1","first-page":"20","article-title":"Effects of membrane protein ANO1 stable overexpression on laryngocarcinoma Hep\u20102 cells","volume":"36","author":"Li YD","year":"2014","journal-title":"Zhongguo yi xue ke xue yuan xue bao Acta Academiae Medicinae Sinicae"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3412"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2012.07.015"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-014-1598-8"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3753"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0115443"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-0475-T"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2015.1102827"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-308988"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-1378"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgu114"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072162"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.22.2.255"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.100105"},{"key":"e_1_2_7_35_1","first-page":"133","volume-title":"SEER survival monograph: cancer survival among adults: US SEER dent Prog, 1988\u20132001, patient and tumor Characteristicsed","author":"Ries LAG","year":"2007"},{"key":"e_1_2_7_36_1","first-page":"1115","article-title":"Preoperative determination of CASA (cancer associated serum antigen) and CA\u2010125 for the discrimination between benign and malignant pelvic tumor mass: a prospective study","volume":"23","author":"Sehouli J","year":"2003","journal-title":"Anticancer Res"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07205"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-2178"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v6.i5.129"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3015"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.02.022"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2644"},{"key":"e_1_2_7_43_1","first-page":"1087","article-title":"Inhibition of phosphatidylinositol 3\u2032\u2010kinase increases efficacy of paclitaxel in in vitro and in vivo ovarian cancer models","volume":"62","author":"Hu L","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/25147"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.24020"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-1248"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2017.08.178"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.90840.2008"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00298.2011"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.232"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-016-1830-9"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.5577"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.31887","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.31887","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T06:57:40Z","timestamp":1751007460000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.31887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,12]]},"references-count":51,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1002\/ijc.31887"],"URL":"https:\/\/doi.org\/10.1002\/ijc.31887","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,12]]},"assertion":[{"value":"2018-05-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}