Evidence map›Paper›PMID 30706544›Full record

ArticleCell proliferation2019

Blockage of SLC31A1-dependent copper absorption increases pancreatic cancer cell autophagy to resist cell death.

Ze Yu, Rongtao Zhou, Yicheng Zhao, Yi Pan, Hao Liang, Jin-San Zhang, Sheng Tai, Liang Jin, Chun-Bo Teng

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell proliferation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed, 2 pooled it
7.8field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

113 citing papers in PubMed, 2 syntheses or guidelines pooled it, 169 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Copper, cuproptosis, and cancer: biology concepts of a novel cell death.Apoptosis : an international journal on programmed cell death · 2026
    Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review

53 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Ze YuCollege of Life Science, Northeast Forestry University, Harbin, China.ORCID https://orcid.org/0000-0002-5849-3413
Rongtao ZhouCollege of Life Science, Northeast Forestry University, Harbin, China.
Yicheng ZhaoCollege of Life Science, Northeast Forestry University, Harbin, China.
Yi PanState Key Laboratory of Natural Medicines, Jiang su Key Laboratory of Drug Screening, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Hao LiangDepartment of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Jin-San ZhangSchool of Pharmaceutical Sciences and the Center for Precision Medicine, The 1st Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
Sheng TaiDepartment of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Liang JinState Key Laboratory of Natural Medicines, Jiang su Key Laboratory of Drug Screening, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Chun-Bo TengCollege of Life Science, Northeast Forestry University, Harbin, China.
Northeast Forestry University · CNChina Pharmaceutical University · CNHarbin Medical University · CNWenzhou Medical University · CN

Funding

Excellent Youth Foundation of Jiangsu Scientific Committee BK20140029Fundamental Research Funds for the Central Universities of China 2572016EAJ3National High Technology Research and Development Program of China 2015AA020314National Natural Science Foundation of China 31472159National Natural Science Foundation of China 8147260Natural Science Foundation of Heilongjiang Province ZD2017001
6 · The paper itself

Abstract

objectivesClinical observations have demonstrated that copper levels elevate in several cancer types, and copper deprivation is shown to inhibit tumour angiogenesis and growth in both animal models and preclinical trials. However, the content of copper in pancreatic duct adenocarcinoma (PDAC) and whether it is a potential therapy target is still unknown. MATERIALS AND

methodsThe levels of copper in PDAC specimens were detected by ICP-MS assays. Copper depletion in Panc-1 or MiaPaCa-2 cells was conducted via copper transporter 1 (SLC31A1) interference and copper chelator tetrathiomolybdate (TM) 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-caused cancer cell quiescence was resolved through mitochondrial dysfunction tests and autophagy studies. The tumour-suppression experiments under the condition of copper block and/or autophagy inhibition were performed both in vitro and in xenografted mice.

resultsSLC31A1-dependent 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 ROS level and decreased ATP 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 TM and autophagy inhibitor CQ increased cell death of cancer cells in vitro and retarded cancer growth in vivo.

conclusionsThese findings reveal that copper deprivation-caused 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-dependent malignant tumours.

Indexed as

AutophagyAdenosine TriphosphateAnimalsApoptosisCarcinoma, Pancreatic DuctalCation Transport ProteinsCell Cycle CheckpointsCell Line, TumorCell ProliferationCopperCopper Transporter 1HumansMaleMicePancreatic NeoplasmsAdenosine TriphosphateCation Transport ProteinsCopperCopper Transporter 1SLC31A1 protein, humanautophagycopperdormancypancreatic cancerSLC31A1

Identifiers

PMID30706544
PMCPMC6496122
OpenAlexW2911581693

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.