Evidence map›Paper›PMID 36398426›Full record

ReviewJournal of cellular and molecular medicine2022

Vascular endothelial growth factor-C in activating vascular endothelial growth factor receptor-3 and chemokine receptor-4 in melanoma adhesion.

Yvette N Hlophe, Anna M Joubert

Open access · goldAbstract readReview
In one paragraph

Review in Journal of cellular and molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

10 citing papers in PubMed, 18 citations in OpenAlex.

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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

2 authors at 1 institution in 1 country.

Yvette N HlopheDepartment of Physiology, University of Pretoria, Pretoria, South Africa.ORCID 0000-0002-3112-2436
Anna M JoubertDepartment of Physiology, University of Pretoria, Pretoria, South Africa.
University of Pretoria · ZA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Vascular endothelial growth factor-C (VEGF-C) binds to receptor vascular endothelial growth factor receptor-3 (VEGFR-3) expressed on lymphatic endothelial and melanoma cells. Binding of VEGF-C to VEGFR-3 enhances receptor phosphorylation that activates mitogen-activated protein kinase (MAP-K) and phosphatidylinositol-3-kinase (PI3K). These signalling pathways regulate cell migration and adhesion in response to internal or external changes. In addition, the overexpression of VEGF-C upregulates chemokine receptor CXCR-4 in tumours (melanoma). CXCR-4 is expressed on cells of the immune system (natural killer cells) and facilitates the migration of leukocytes in response to the CXCL12 ligand. The latter is expressed by lymphatic endothelial cells and by stromal cells in the tumour microenvironment (TME). The gradient established between CXCR-4 expressed on tumour cells and CXCL12 produced by stromal and lymphatic endothelial cells enhances tumour cell metastasis. 3-(4-Dimethylamino-naphthalen-1-ylmethylene)-1, 3-dihydroindol-2-one, MAZ-51, is an indolinone-based synthetic molecule that inhibits the phosphorylation of the tyrosine kinase receptor VEGFR-3. CTCE-9908, a CXCR-4 antagonist derived from human CXCL12, hinders receptor phosphorylation and the subsequent signalling pathways that would be activated. VEGF-C is stimulated by transforming growth factor-beta 1 (TGF-β1), which facilitates cell-cell and cell-matrix adhesion by regulating cadherins through the activation of focal adhesion kinase (FAK) and mediates paxillin upregulation. Increased VEGF-C protein levels stimulated by TGF-β bound to VEGFR-3 impact on intracellular pathways that promote tumour cell adhesion. In addition, increased VEGF-C protein levels lead to enhanced CXCR-4 protein expression. Therefore, effective blocking of VEGR-3 and CXCR-4 may inhibit tumour cell metastasis by hampering intracellular proteins promoting adhesion.

Indexed as

MelanomaVascular Endothelial Growth Factor CVascular Endothelial Growth Factor Receptor-3Endothelial CellsHumansReceptors, CXCR4Tumor MicroenvironmentCXCR4 protein, humanReceptors, CXCR4Vascular Endothelial Growth Factor CVascular Endothelial Growth Factor Receptor-3

Identifiers

PMID36398426
PMCPMC9716217
OpenAlexW4309277447

What Socratic 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 Socratic graph.