{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:36:55Z","timestamp":1792571815874,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,2,24]],"date-time":"2016-02-24T00:00:00Z","timestamp":1456272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000147","name":"Canadian Cancer Society","doi-asserted-by":"publisher","award":["701080"],"award-info":[{"award-number":["701080"]}],"id":[{"id":"10.13039\/501100000147","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Although aldosterone is a known regulator of renal and cardiovascular function, its role as a regulator of cancer growth and spread has not been widely considered. This study tested the hypothesis that aldosterone regulates cancer cell growth\/spread\n                    <jats:italic>via<\/jats:italic>\n                    G protein\u2010coupled estrogen receptor (GPER) activation.\n                    <jats:italic>In vitro<\/jats:italic>\n                    in murine renal cortical adenocarcinoma (RENCA) cells, a widely used murine\n                    <jats:italic>in vitro<\/jats:italic>\n                    model for the study of renal cell adenocarcinoma, aldosterone increased RENCA cell proliferation to a maximum of 125 \u00b1 3% of control at a concentration of 10 nM, an effect blocked by the GPER antagonist G15 or by GPER knockdown using short interfering (sh) RNA techniques. Further, aldosterone increased RENCA cell migration to a maximum of 170 \u00b1 20% of control at a concentration of 100 nM, an effect also blocked by G15 or by GPER down\u2010regulation.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , after orthotopic RENCA cell renal transplantation, pulmonary tumor spread was inhibited by pharmacologic blockade of aldosterone effects with spironolactone (percentage of lung occupied by metastasis: control = 68 \u00b1 13, spironolactone = 26 \u00b1 8,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05) or inhibition of aldosterone synthesis with a high dietary salt diet (percentage of lung: control = 44 \u00b1 6, high salt = 12 \u00b1 3,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05), without reducing primary tumor size. Additionally, adrenalectomy significantly reduced the extent of pulmonary tumor spread, whereas aldosterone infusion recovered pulmonary metastatic spread toward baseline levels. Finally, inhibition of GPER either with the GPER antagonist G15 or by GPER knockdown comparably inhibited RENCA cell pulmonary metastatic cancer spread. Taken together, these findings provide strong evidence for aldosterone serving a causal role in renal cell cancer regulation\n                    <jats:italic>via<\/jats:italic>\n                    its GPER receptor; thus, antagonism of GPER represents a potential new target for treatment to reduce metastatic spread.\u2014Feldman, R. D., Ding, Q., Hussain, Y., Limbird, L. E., Pickering, J. G., Gros, R. Aldosterone mediates metastatic spread of renal cancer\n                    <jats:italic>via<\/jats:italic>\n                    the G protein\u2010coupled estrogen receptor (GPER). FASEB J. 30, 2086\u20132096 (2016).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.15-275552","type":"journal-article","created":{"date-parts":[[2016,2,24]],"date-time":"2016-02-24T23:36:47Z","timestamp":1456357007000},"page":"2086-2096","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Aldosterone mediates metastatic spread of renal cancer\n                    <i>via<\/i>\n                    the G protein\u2010coupled estrogen receptor (GPER)"],"prefix":"10.1096","volume":"30","author":[{"given":"Ross D.","family":"Feldman","sequence":"first","affiliation":[{"name":"Discipline of Medicine Memorial University of Newfoundland St. John's Newfoundland and Labrador Canada"},{"name":"Molecular Medicine Group, Robarts Research Institute London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingming","family":"Ding","sequence":"additional","affiliation":[{"name":"Discipline of Medicine Memorial University of Newfoundland St. John's Newfoundland and Labrador Canada"},{"name":"Molecular Medicine Group, Robarts Research Institute London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasin","family":"Hussain","sequence":"additional","affiliation":[{"name":"Molecular Medicine Group, Robarts Research Institute London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee E.","family":"Limbird","sequence":"additional","affiliation":[{"name":"Department of Life and Physical Sciences Fisk University Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Geoffrey","family":"Pickering","sequence":"additional","affiliation":[{"name":"Molecular Medicine Group, Robarts Research Institute London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Gros","sequence":"additional","affiliation":[{"name":"Molecular Medicine Group, Robarts Research Institute London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2011.06.049"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2010.46"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.4103\/1477-3163.127638"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.12157"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5565"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2011.04.002"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-789X.2011.00914.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-013-0330-y"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a009157"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01804982"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/09513590903511521"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2009.09.014"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90428.2008"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000339500"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1677\/JME-09-0031"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2011.12.023"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.161653"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00072.2014"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.257204"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1998.5095"},{"key":"e_1_2_7_22_1","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1006\/geno.1997.4972","article-title":"Identification of a gene (GPR30) with homology to the G\u2010protein\u2010coupled receptor superfamily associated with estrogen receptor expression in breast cancer","volume":"45","author":"Canned C.","year":"1997","journal-title":"Genomics"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7734"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1106943"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend.16.1.0758"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1124\/mi.5.3.5"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-0760(01)00190-X"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2001-211445"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2005-0280"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2909"},{"issue":"386","key":"e_1_2_7_31_1","first-page":"e381","article-title":"GPR30: a novel indicator of poor survival for endometrial carcinoma","volume":"196","author":"Smith H. 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