Evidence map›Paper›PMID 21602890›Full record

ArticleOncogene2011

Loss of Mel-18 induces tumor angiogenesis through enhancing the activity and expression of HIF-1α mediated by the PTEN/PI3K/Akt pathway.

J H Park, J Y Lee, D H Shin, K S Jang, H J Kim, Gu Kong

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 2 pooled it
1.8field-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

43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 61 citations in OpenAlex.

  1. Pooled it
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  11. Critical Roles of Polycomb Repressive Complexes in Transcription and Cancer.International journal of molecular sciences · 2022
    Review
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  18. Lymph Liquid Biopsy for Detection of Cancer Stem Cells.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2021
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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 1 country.

J H ParkDepartment of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
J Y Lee
D H Shin
K S Jang
H J Kim
Gu Kong
Hanyang University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mel-18 has been implicated in several processes in tumor progression, in which the Akt pathway is involved as an important key molecular event. However, the function of Mel-18 in human cancers has not been fully established yet. Here, we examined the effect of Mel-18 on tumor angiogenesis in human breast cancer, and found that Mel-18 was a novel regulator of HIF-1α. Mel-18 negatively regulated the HIF-1α expression and its target gene VEGF transcription during both normoxia and hypoxia. We demonstrated that Mel-18 regulated the HIF-1α expression and activity via the PI3K/Akt pathway. Loss of Mel-18 downregulated Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression, consequently activating the PI3K/Akt/MDM2 pathway, and leading to an increase of HIF-1α protein level. Mel-18 modulated the HIF-1α transcriptional activity via regulating the cytoplasmic retention of FOXO3a, a downstream effector of Akt, and recruitment of HIF-1α/CBP complex to the VEGF promoter. Furthermore, our data shows that Mel-18 blocked tumor angiogenesis both in vitro and in vivo. Mel-18 overexpression inhibited in vitro tube formation in human umbilical endothelial cells (HUVECs). Xenografts in NOD/SCID mice derived from stably Mel-18 knocked down MCF7 human breast cancer cells showed increased tumor volume, microvessel density, and phospho-Akt and HIF-1α expression levels. In conclusion, our findings provide that Mel-18 is a novel regulator of tumor angiogenesis through regulating HIF-1α and its target VEGF expressions mediated by the PTEN/PI3K/Akt pathway, suggesting a new tumor-suppressive role of Mel-18 in human breast cancer.

Indexed as

AnimalsBreast NeoplasmsCell Line, TumorFemaleForkhead Box Protein O3Forkhead Transcription FactorsGene Knockdown TechniquesHumansHypoxia-Inducible Factor 1, alpha SubunitMiceMice, Inbred NODNeovascularization, PathologicPhosphatidylinositol 3-KinasePolycomb Repressive Complex 1Proto-Oncogene Proteins c-aktPTEN PhosphohydrolaseForkhead Box Protein O3Forkhead Transcription FactorsFOXO3 protein, humanHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitPCGF2 protein, humanPhosphatidylinositol 3-KinasePolycomb Repressive Complex 1Proto-Oncogene Proteins c-aktPTEN PhosphohydrolasePTEN protein, humanRepressor ProteinsVascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID21602890
OpenAlexW2016910890

What OpenQuestion holds

Textmetadata
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.