{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:51:21Z","timestamp":1791474681343,"version":"4.3.4"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>N\u2010myc downstream\u2010regulated gene 2<\/jats:italic>\n                    (\n                    <jats:italic>NDRG2<\/jats:italic>\n                    ) is a candidate tumor suppressor in various cancers, including adult T\u2010cell leukemia\/lymphoma (ATLL). NDRG2, as a stress\u2010responsive protein, is induced by several stress\u2010related signaling pathways and NDRG2 negatively regulates various signal transduction pathways. Although it has not been found to function alone, NDRG2 binds serine\/threonine protein phosphatase 2A (PP2A), generating a complex that is involved in the regulation of various target proteins. The main function of NDRG2 is to maintain cell homeostasis by suppressing stress\u2010induced signal transduction; however, in cancer, genomic deletions and\/or promoter methylation may inhibit the expression of NDRG2, resulting in enhanced tumor development through overactivated signal transduction pathways. A wide variety of tumors develop in\n                    <jats:italic>Ndrg2<\/jats:italic>\n                    \u2010deficient mice, including T\u2010cell lymphoma, liver, lung and other tumors, the characteristics of which are similar to those in\n                    <jats:italic>Pten\u2010<\/jats:italic>\n                    deficient mice. In particular, PTEN is a target molecule of the NDRG2\/PP2A complex, which enhances PTEN phosphatase activity by dephosphorylating residues in the PTEN C\u2010terminal region. In ATLL cells, loss of NDRG2 expression leads to the failed recruitment of PP2A to PTEN, resulting in the inactivation of PTEN phosphatase with phosphorylation, ultimately leading to the activation of PI3K\/AKT. Thus, NDRG2, as a PP2A adaptor, regulates the global phosphorylation of important signaling molecules. Moreover, the downregulation of NDRG2 expression by long\u2010term stress\u2010induced methylation is directly correlated with the development of ATLL and other cancers. Thus, NDRG2 might be important for the development of stress\u2010induced leukemia and other cancers and has become an important target for novel molecular therapies.\n                  <\/jats:p>","DOI":"10.1111\/cas.14716","type":"journal-article","created":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T21:43:56Z","timestamp":1604094236000},"page":"22-30","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Pathophysiological significance of N\u2010myc downstream\u2010regulated gene 2 in cancer development through protein phosphatase 2A phosphorylation regulation"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2245-9950","authenticated-orcid":false,"given":"Kazuhiro","family":"Morishita","sequence":"first","affiliation":[{"name":"Medical Sciences Faculty of Medicine University of Miyazaki Miyazaki 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