Evidence map›Paper›PMID 30834688›Full record

ArticleJournal of cellular and molecular medicine2019

Increase in the nuclear localization of PTEN by the Toxoplasma GRA16 protein and subsequent induction of p53-dependent apoptosis and anticancer effect.

Sang-Gyun Kim, Seung-Hwan Seo, Ji-Hun Shin, Jung-Pyo Yang, Sang Hyung Lee, Eun-Hee Shin

Open access · goldAbstract read
In one paragraph

Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 2 pooled it
2.2field-weighted citation impact, top 15% 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

17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.

  1. Pathogens (Basel, Switzerland) · 2026
    Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Biomolecules & therapeutics · 2025
    Article
  6. Article
  7. Science advances · 2024
    Article
  8. Parasites revive hope for cancer therapy.European journal of medical research · 2024
    Review
  9. Article
  10. Article
  11. Article
  12. Secreted Effectors Modulating Immune Responses toLife (Basel, Switzerland) · 2021
    Review
  13. Review
  14. Computational and structural biotechnology journal · 2021
    Article
  15. International journal of molecular sciences · 2020
    Article
  16. Article
  17. 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

6 authors at 1 institution in 2 countries.

Sang-Gyun KimDepartment of Parasitology and Tropical Medicine, Seoul National University College of Medicine and Institute of Endemic Diseases, Seoul, Republic of Korea.
Seung-Hwan SeoDepartment of Parasitology and Tropical Medicine, Seoul National University College of Medicine and Institute of Endemic Diseases, Seoul, Republic of Korea.
Ji-Hun ShinDepartment of Parasitology and Tropical Medicine, Seoul National University College of Medicine and Institute of Endemic Diseases, Seoul, Republic of Korea.
Jung-Pyo YangDepartment of Parasitology and Tropical Medicine, Seoul National University College of Medicine and Institute of Endemic Diseases, Seoul, Republic of Korea.
Sang Hyung LeeDepartment of Neurosurgery, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
Eun-Hee ShinDepartment of Parasitology and Tropical Medicine, Seoul National University College of Medicine and Institute of Endemic Diseases, Seoul, Republic of Korea.ORCID 0000-0003-1215-1079
Seoul National University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This study investigated the efficacy of Toxoplasma GRA16, which binds to herpes virus-associated ubiquitin-specific protease (HAUSP), in anticancer treatment, and whether the expression of GRA16 in genetically modified hepatocellular carcinoma (HCC) cells (GRA16-p53-wild HepG2 and GRA16-p53-null Hep3B) regulates PTEN because alterations in phosphatase and tensin homologue (PTEN) and p53 are vital in liver carcinogenesis and the abnormal p53 gene appears in HCC. For this purpose, we established the GRA16 cell lines using the pBABE retrovirus system, assessed the detailed mechanism of PTEN regulation in vitro and established the anticancer effect in xenograft mice. Our study showed that cell proliferation, antiapoptotic factors, p-AKT/AKT ratio, cell migration and invasive activity were decreased in GRA16-stable HepG2 cells. Conversely, the apoptotic factors PTEN and p53 and apoptotic cells were elevated in GRA16-stable HepG2 cells but not in Hep3B cells. The change in MDM2 was inconspicuous in both HepG2 and Hep3B; however, the PTEN level was remarkably elevated in HepG2 but not in Hep3B. HAUSP-bound GRA16 preferentially increased p53 stabilization by the nuclear localization of PTEN rather than MDM2-dependent mechanisms. These molecular changes appeared to correlate with the decreased tumour mass in GRA16-stable-HepG2 cell-xenograft nude mice. This study establishes that GRA16 is a HAUSP inhibitor that targets the nuclear localization of PTEN and induces the anticancer effect in a p53-dependent manner. The efficacy of GRA16 could be newly highlighted in HCC treatment in a p53-dependent manner.

Indexed as

AnimalsApoptosisCarcinogenesisCarcinoma, HepatocellularCell MovementCell ProliferationHep G2 CellsHeterograftsHumansLiverLiver NeoplasmsMiceProtein BindingProtozoan ProteinsPTEN PhosphohydrolaseToxoplasmaProtozoan ProteinsPTEN PhosphohydrolasePTEN protein, humanTP53 protein, humanTumor Suppressor Protein p53Ubiquitin-Specific Peptidase 7USP7 protein, humancell cycle arrestGRA16-stable cell lineHAUSPHep3Bhepatocellular carcinomaHepG2p53PTENToxoplasma GRA16USP7

Identifiers

PMID30834688
PMCPMC6484329
OpenAlexW2920129146

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.