Evidence map›Paper›PMID 31311812›Full record

ArticleCancer research2019

Metastasis Suppressors NME1 and NME2 Promote Dynamin 2 Oligomerization and Regulate Tumor Cell Endocytosis, Motility, and Metastasis.

Imran Khan, Brunilde Gril, Patricia S Steeg

Open access · greenAbstract read
In one paragraph

Article in Cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

41 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Histidine Phosphorylation: Protein Kinases and Phosphatases.International journal of molecular sciences · 2024
    Review
  6. Review
  7. Article
  8. The Proteomic Analysis of Cancer-Related Alterations in the Human Unfoldome.International journal of molecular sciences · 2024
    Article
  9. A perspective on the metastasis suppressor field.Cancer metastasis reviews · 2023
    Review
  10. Review
  11. Endocytosis in cancer and cancer therapy.Nature reviews. Cancer · 2023
    Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Long-chain fatty acyl coenzyme A inhibits NME1/2 and regulates cancer metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  18. Review
  19. Article
  20. Article
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

3 authors at 1 institution in 1 country.

Imran KhanWomen's Malignancies Branch, Center for Cancer Research, NCI, Bethesda, Maryland. imran.khan@nih.gov.
Brunilde GrilWomen's Malignancies Branch, Center for Cancer Research, NCI, Bethesda, Maryland.
Patricia S SteegWomen's Malignancies Branch, Center for Cancer Research, NCI, Bethesda, Maryland.
Center for Cancer Research · US

Funding

Molecular Biology of the Metastatic PhenotypeZIASC000892 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI STEEG, PATRICIA SCHRIVER · 2009 to 2023
$8.4M
Intramural NIH HHS ZIA SC000892
6 · The paper itself

Abstract

NM23 (NME) is a metastasis suppressor that significantly reduces metastasis without affecting primary tumor size, however, the precise molecular mechanisms are not completely understood. We examined the role of dynamin (DNM2), a GTPase regulating membrane scission of vesicles in endocytosis, in NME1 and NME2 regulation of tumor cell motility and metastasis. Overexpression of NMEs in MDA-MB-231T and MDA-MB-435 cancer cell lines increased endocytosis of transferrin and EGF receptors (TfR and EGFR) concurrent with motility and migration suppression. The internalized vesicles, costained with Rab5, had AP2 depleted from the cell surface and exhibited increased Rab5-GTP levels, consistent with endocytosis. Dynamin inhibitors Iminodyn-22 and Dynole-34-2, or shRNA-mediated downregulation of DNM2, impaired NME's ability to augment endocytosis or suppress tumor cell motility. In a lung metastasis assay, NME1 overexpression failed to significantly suppress metastasis in the DNM2 knockdown MDA-MB-231T cells. Using the EGF-EGFR signaling axis as a model in MDA-MB-231T cells, NME1 decreased pEGFR and pAkt expression in a DNM2-dependent manner, indicating the relevance of this interaction for downstream signaling. NME-DNM2 interaction was confirmed in two-way coimmunoprecipitations. Transfection of a NME1 site-directed mutant lacking histidine protein kinase activity but retaining nucleoside diphosphate kinase (NDPK) activity showed that the NDPK activity of NME was insufficient to promote endocytosis or inhibit EGFR signaling. We show that addition of NME1 or NME2 to DNM2 facilitates DNM2 oligomerization and increases GTPase activity, both required for vesicle scission. NME-DNM2 interaction may contribute to metastasis suppression by altering tumor endocytic and motility phenotypes. SIGNIFICANCE: NME1 suppresses metastasis via changes in tumor endocytosis and motility, mediated by dynamin (DNM2) GTPase activity.

Indexed as

Cell MovementEndocytosisAnimalsApoptosisBreast NeoplasmsCell ProliferationDynamin IIFemaleHumansMiceMice, Inbred BALB CMice, NudeNeoplasm MetastasisNM23 Nucleoside Diphosphate KinasesProtein MultimerizationTumor Cells, CulturedDNM2 protein, humanDynamin IINM23 Nucleoside Diphosphate KinasesNME1 protein, humanNME2 protein, human

Identifiers

PMID31311812
PMCPMC8288561
OpenAlexW2957928248

What OpenQuestion holds

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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.