Evidence map›Paper›PMID 37169211›Full record

ArticleCellular signalling2023

Angiopoietin-like 4 induces head and neck squamous cell carcinoma cell migration through the NRP1/ABL1/PXN pathway.

Eman Hefni, Deepak Menon, Tao Ma, Emmanuel B Asiedu, Ahmed Sultan, Timothy Meiller, Abraham Schneider, Akrit Sodhi, Silvia Montaner

Open access · greenAbstract read
In one paragraph

Article in Cellular signalling, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 14% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.

  1. Models of Oral Epithelial Dysplasia: A Systematic Review and Temporal Analysis.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2026
    Pooled it
  2. Article
  3. Targeting the ANGPTL4/NRP1/ABL1/RAD51 axis reverses cisplatin resistance by impairing DNA damage repair in head and neck cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Angiopoietin-like 4 is upregulated by amphiregulin and activates cell proliferation and migration through p38 kinase in head and neck squamous cell carcinoma.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2024
    Article
  9. Investigating the Effects ofAvicenna journal of medical biotechnology
    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

9 authors at 2 institutions in 2 countries.

Eman HefniDepartment of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, Baltimore, MD 21201, USA; Department of Basic and Clinical Oral Sciences, College of Dentistry, Umm Al Qura University, Makkah, Saudi Arabia.
Deepak MenonDepartment of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, Baltimore, MD 21201, USA.
Tao MaDepartment of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, Baltimore, MD 21201, USA.
Emmanuel B AsieduDepartment of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, Baltimore, MD 21201, USA.
Ahmed SultanDepartment of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, Baltimore, MD 21201, USA; Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD 21201, USA.
Timothy MeillerDepartment of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, Baltimore, MD 21201, USA; Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD 21201, USA.
Abraham SchneiderDepartment of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, Baltimore, MD 21201, USA; Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD 21201, USA.
Akrit SodhiWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Silvia MontanerDepartment of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, Baltimore, MD 21201, USA; Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD 21201, USA. Electronic address: smontaner@umaryland.edu.
University of Maryland, Baltimore · USJohns Hopkins University · US

Funding

Training Grant in Cancer BiologyT32CA154274 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI Toni M Antalis, CURT I CIVIN · 2011 to 2026
$6.8M
Molecular Targets for the Prevention and Treatment of Kaposi's SarcomaR01CA119911 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI MONTANER, SILVIA V · 2007 to 2011
$1.4M
In Vivo Fluorescence and Bioluminescence Imager with CTS10OD030430 · OD · UNIVERSITY OF MARYLAND BALTIMORE · PI LAPIDUS, RENA · 2021 to 2021
$600k
NCI NIH HHS R01 CA119911NCI NIH HHS T32 CA154274NIH HHS S10 OD030430
6 · The paper itself

Abstract

objectivesThe molecular mechanisms whereby angiopoietin-like 4 (ANGPTL4), a pluripotent protein implicated in cancer development, contributes to head and neck squamous cell carcinoma (HNSCC) growth and dissemination are unclear. MATERIALS AND

methodsWe investigated ANGPTL4 expression in human normal oral keratinocytes (NOKs), dysplastic oral keratinocytes (DOKs), oral leukoplakia cells (LEUK1), and HNSCC cell lines, as well as in tissue biopsies from patients with oral dysplasia, and primary and metastatic HNSCC. We further examined the contribution of ANGPTL4 cancer progression in an HNSCC orthotopic floor-of mouth tumor model and the signaling pathways linking ANGPTL4 to cancer cell migration.

resultsANGPTL4 expression was upregulated in premalignant DOKs and HNSCC cell lines compared to NOKs and was increased in tissue biopsies from patients with oral dysplasia, as well as in primary and metastatic HNSCC. We also observed that downregulation of ANGPTL4 expression inhibited primary and metastatic cancer growth in an HNSCC orthotopic tumor model. Interestingly, ANGPTL4 binding to the neuropilin1 (NRP1) receptor led to phosphorylation of the focal adhesion protein, paxillin (PXN), and tumor cell migration; this was dependent on the tyrosine kinase ABL1. Treatment with the ABL1 inhibitor, dasatinib and small interfering RNA silencing of NRP1 or ABL1 expression blocked PXN phosphorylation and tumor cell migration.

conclusionOur findings suggest an early, sustained, and angiogenesis-independent autocrine role for ANGPTL4 in HNSCC progression and expose ANGPTL4/NRP1/ABL1/PXN as an early molecular marker and vulnerable target for the prevention of HNSCC growth and metastasis.

Indexed as

Carcinoma, Squamous CellHead and Neck NeoplasmsAngiopoietin-Like Protein 4AngiopoietinsCell Line, TumorCell MovementHumansNeuropilin-1PaxillinProto-Oncogene Proteins c-ablSquamous Cell Carcinoma of Head and NeckABL1 protein, humanAngiopoietin-Like Protein 4AngiopoietinsANGPTL4 protein, humanNeuropilin-1NRP1 protein, humanPaxillinProto-Oncogene Proteins c-ablPXN protein, humanABL proto-oncogene 1Angiopoietin-like 4Cell migrationHead and neck squamous cell carcinomaNeuropilinOral dysplasiaPaxillin

Identifiers

PMID37169211
PMCPMC11129037
OpenAlexW4375951653

What Socratic holds

Textmetadata
LicenceTDM
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.