{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:35:10Z","timestamp":1792596910973,"version":"4.5.0"},"reference-count":38,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009338","name":"Marine Biodiversity Institute of Korea","doi-asserted-by":"publisher","award":["2022M00400"],"award-info":[{"award-number":["2022M00400"]}],"id":[{"id":"10.13039\/501100009338","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Glioblastoma multiforme (GBM) is a fast-growing and aggressive type of brain cancer. Unlike normal brain cells, GBM cells exhibit epithelial\u2013mesenchymal transition (EMT), which is a crucial biological process in embryonic development and cell metastasis, and are highly invasive. Copper reportedly plays a critical role in the progression of a variety of cancers, including brain, breast, and lung cancers. However, excessive copper is toxic to cells. D-penicillamine (DPA) and triethylenetetramine (TETA) are well-known copper chelators and are the mainstay of treatment for copper-associated diseases. Following treatment with copper sulfate and DPA, GBM cells showed inhibition of proliferation and suppression of EMT properties, including reduced expression levels of N-cadherin, E-cadherin, and Zeb, which are cell markers associated with EMT. In contrast, treatment with copper sulfate and TETA yielded the opposite effects in GBM. Genes, including TGF-\u03b2, are associated with an increase in copper levels, implying their role in EMT. To analyze the invasion and spread of GBM, we used zebrafish embryos xenografted with the GBM cell line U87. The invasion of GBM cells into zebrafish embryos was markedly inhibited by copper treatment with DPA. Our findings suggest that treatment with copper and DPA inhibits proliferation and EMT through a mechanism involving TGF-\u03b2\/Smad signaling in GBM. Therefore, DPA, but not TETA, could be used as adjuvant therapy for GBM with high copper concentrations.<\/jats:p>","DOI":"10.3390\/molecules27248851","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T03:21:52Z","timestamp":1670988112000},"page":"8851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Effect of Copper Chelators via the TGF-\u03b2 Signaling Pathway on Glioblastoma Cell Invasion"],"prefix":"10.3390","volume":"27","author":[{"given":"Heabin","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Genetic Resources, National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0305-3250","authenticated-orcid":false,"given":"Seonmi","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Genetic Resources, National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Gyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Radiation Biology, Environmental Safety Assessment Research Division, Korea Atomic Energy Research Institute, Daejeon 34057, Republic of Korea"},{"name":"Department of Radiation Science and Technology, Korea University of Science and Technology, Daejeon 34113, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6607-4449","authenticated-orcid":false,"given":"Rae-Kwon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Radiation Biology, Environmental Safety Assessment Research Division, Korea Atomic Energy Research Institute, Daejeon 34057, Republic of Korea"},{"name":"Department of Radiation Science and Technology, Korea University of Science and Technology, Daejeon 34113, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon-Jee","family":"Kahm","sequence":"additional","affiliation":[{"name":"Department of Radiation Biology, Environmental Safety Assessment Research Division, Korea Atomic Energy Research Institute, Daejeon 34057, Republic of Korea"},{"name":"Department of Radiation Science and Technology, Korea University of Science and Technology, Daejeon 34113, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9870-0923","authenticated-orcid":false,"given":"Seung-Hyun","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Genetic Resources, National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jei Ha","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Genetic Resources, National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Khasraw, M., Ameratunga, M.S., Grant, R., Wheeler, H., and Pavlakis, N. 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