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However, the content of copper in pancreatic duct adenocarcinoma (\n                      <jats:styled-content style=\"fixed-case\">PDAC<\/jats:styled-content>\n                      ) and whether it is a potential therapy target is still unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      The levels of copper in\n                      <jats:styled-content style=\"fixed-case\">PDAC<\/jats:styled-content>\n                      specimens were detected by\n                      <jats:styled-content style=\"fixed-case\">ICP<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\n                      assays. Copper depletion in Panc\u20101 or MiaPaCa\u20102 cells was conducted via copper transporter 1 (\n                      <jats:styled-content style=\"fixed-case\">SLC<\/jats:styled-content>\n                      31A1) interference and copper chelator tetrathiomolybdate (\n                      <jats:styled-content style=\"fixed-case\">TM<\/jats:styled-content>\n                      ) treatment. The effects of copper deprivation on cancer cells were evaluated by cell proliferation, migration, invasion, colony formation and cell apoptosis. The mechanism of copper deprivation\u2010caused cancer cell quiescence was resolved through mitochondrial dysfunction tests and autophagy studies. The tumour\u2010suppression experiments under the condition of copper block and\/or autophagy inhibition were performed both in vitro and in xenografted mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">SLC<\/jats:styled-content>\n                      31A1\u2010dependent copper levels are correlated with the malignant degree of pancreatic cancer. Blocking copper absorption could inhibit pancreatic cancer progression but did not increase cell death. We found that copper deprivation increased mitochondrial\n                      <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>\n                      level and decreased\n                      <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\n                      level, which rendered cancer cells in a dormant state. Strikingly, copper deprivation caused an increase in autophagy to resist death of pancreatic cancer cells. Simultaneous treatment with\n                      <jats:styled-content style=\"fixed-case\">TM<\/jats:styled-content>\n                      and autophagy inhibitor\n                      <jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content>\n                      increased cell death of cancer cells in vitro and retarded cancer growth in vivo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings reveal that copper deprivation\u2010caused cell dormancy and the increase in autophagy is a reason for the poor clinical outcome obtained from copper depletion therapies for cancers. Therefore, the combination of autophagy inhibition and copper depletion is potentially a novel strategy for the treatment of pancreatic cancer and other copper\u2010dependent malignant tumours.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cpr.12568","type":"journal-article","created":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T23:09:45Z","timestamp":1548976185000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":159,"title":["Blockage of SLC31A1\u2010dependent copper absorption increases pancreatic cancer cell autophagy to resist cell death"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5849-3413","authenticated-orcid":false,"given":"Ze","family":"Yu","sequence":"first","affiliation":[{"name":"College of Life Science Northeast Forestry University Harbin 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