{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:54:52Z","timestamp":1786978492198,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["109015"],"award-info":[{"award-number":["109015"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The surface expression of Na\/K\u2010ATPase \u03b11 (NKA) is significantly reduced in primary prostate tumors and further decreased in bone metastatic lesions. Here, we show that the loss of cell surface expression of NKA induces epithelial\u2013mesenchymal transition (EMT) and promotes metastatic potential and tumor growth of prostate cancer (PCa) by decreasing the expression of E\u2010cadherin and increasing c\u2010Myc expression via the activation of Src\/FAK pathways. Mechanistically, reduced surface expression of NKA in PCa is due to increased endocytosis through the activation of NKA\/Src receptor complex. Using a high\u2010throughput NKA ligand\u2010screening platform, we have discovered MB5 as an inverse agonist of the NKA\/Src receptor complex, capable of blocking the endocytosis of NKA. MB5 treatment increased NKA expression and E\u2010cadherin in PCa cells, which reversed EMT and consequently decreased the invasion and growth of spheroid models and tumor xenografts. Thus, we have identified a hitherto unrecognized mechanism that regulates EMT and invasiveness of PCa and demonstrated for the first time the feasibility of identifying inverse agonists of receptor NKA\/Src complex and their potential utility as anticancer drugs. We, therefore, conclude that cell surface expression of \u03b11 NKA can be targeted for the development of new therapeutics against aggressive PCa and that MB5 may serve as a prototype for drug development against EMT in metastatic PCa.<\/jats:p>","DOI":"10.1002\/pros.24144","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T09:08:33Z","timestamp":1620378513000},"page":"667-682","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Inverse agonism at the Na\/K\u2010ATPase receptor reverses EMT in prostate cancer cells"],"prefix":"10.1002","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4463-7914","authenticated-orcid":false,"given":"Moumita","family":"Banerjee","sequence":"first","affiliation":[{"name":"Marshall Institute for Interdisciplinary Research (MIIR) Marshall University  Huntington West Virginia 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