Evidence map›Paper›PMID 34773645›Full record

ArticleThe British journal of dermatology2022

Melanoma secretion of transforming growth factor-β2 leads to loss of epidermal AMBRA1 threatening epidermal integrity and facilitating tumour ulceration.

I Cosgarea, A T McConnell, T Ewen, D Tang, D S Hill, M Anagnostou, M Elias, R A Ellis, A Murray, L C Spender and 9 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The British journal of dermatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. The tumor immune microenvironment in primary cutaneous melanoma.Archives of dermatological research · 2025
    Review
  5. Contribution of Keratinocytes in Skin Cancer Initiation and Progression.International journal of molecular sciences · 2024
    Review
  6. AMBRA1 levels predict resistance to MAPK inhibitors in melanoma.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 8 institutions in 2 countries.

I CosgareaTranslation and Clinical Research Institute, The Medical School, Newcastle University, Newcastle, UK.
A T McConnellTranslation and Clinical Research Institute, The Medical School, Newcastle University, Newcastle, UK.
T EwenTranslation and Clinical Research Institute, The Medical School, Newcastle University, Newcastle, UK.
D TangTranslation and Clinical Research Institute, The Medical School, Newcastle University, Newcastle, UK.
D S HillTranslation and Clinical Research Institute, The Medical School, Newcastle University, Newcastle, UK.
M AnagnostouTranslation and Clinical Research Institute, The Medical School, Newcastle University, Newcastle, UK.
M EliasTranslation and Clinical Research Institute, The Medical School, Newcastle University, Newcastle, UK.
R A EllisTranslation and Clinical Research Institute, The Medical School, Newcastle University, Newcastle, UK.ORCID 0000-0001-6305-2121
A MurrayTranslation and Clinical Research Institute, The Medical School, Newcastle University, Newcastle, UK.
L C SpenderJacqui Wood Cancer Centre & Nine Wells Hospital and Medical School, University of Dundee, Dundee, UK.
P GiglioDepartment of Biology, University of Rome 'Tor Vergata', Rome, Italy.
M GagliardiDepartment Health Sciences, and Centre for Translational Research on Autoimmune and Allergic Disease (CAAD), University of Piemonte Orientale, Novara, Italy.
A GreenwoodTranslation and Clinical Research Institute, The Medical School, Newcastle University, Newcastle, UK.
M PiacentiniDepartment of Biology, University of Rome 'Tor Vergata', Rome, Italy.
G J InmanCRUK Beatson Institute and Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.ORCID 0000-0002-6264-4253
G M FimiaDepartment of Epidemiology, Preclinical Research, and Advanced Diagnostics, National Institute for Infectious Diseases 'L. Spallanzani' IRCCS, Rome, Italy.
M CorazzariDepartment Health Sciences, and Centre for Translational Research on Autoimmune and Allergic Disease (CAAD), University of Piemonte Orientale, Novara, Italy.
J L ArmstrongTranslation and Clinical Research Institute, The Medical School, Newcastle University, Newcastle, UK.ORCID 0000-0002-5822-0597
P E LovatTranslation and Clinical Research Institute, The Medical School, Newcastle University, Newcastle, UK.ORCID 0000-0002-6657-6825
Newcastle University · GBOJ-Bio (United Kingdom) · GBUniversità degli Studi del Piemonte Orientale “Amedeo Avogadro” · ITUniversity of Rome Tor Vergata · ITUniversity of Sunderland · GBCancer Research UK Scotland Institute · GBIstituti di Ricovero e Cura a Carattere Scientifico · ITUniversity of Dundee · GB

Funding

Cancer Research UK 29802Chief Scientist Office TCS/19/18National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/L002000/1Worldwide Cancer Research 11-078
6 · The paper itself

Abstract

backgroundFor patients with early American Joint Committee on Cancer (AJCC)-stage melanoma the combined loss of the autophagy regulatory protein AMBRA1 and the terminal differentiation marker loricrin in the peritumoral epidermis is associated with a significantly increased risk of metastasis.

objectivesThe aim of the present study was to evaluate the potential contribution of melanoma paracrine transforming growth factor (TGF)-β signalling to the loss of AMBRA1 in the epidermis overlying the primary tumour and disruption of epidermal integrity.

methodsImmunohistochemistry was used to analyse AMBRA1 and TGF-β2 in a cohort of 109 AJCC all-stage melanomas, and TGF-β2 and claudin-1 in a cohort of 30 or 42 AJCC stage I melanomas, respectively, with known AMBRA1 and loricrin (AMLo) expression. Evidence of pre-ulceration was analysed in a cohort of 42 melanomas, with TGF-β2 signalling evaluated in primary keratinocytes.

resultsIncreased tumoral TGF-β2 was significantly associated with loss of peritumoral AMBRA1 (P < 0·05), ulceration (P < 0·001), AMLo high-risk status (P < 0·05) and metastasis (P < 0·01). TGF-β2 treatment of keratinocytes resulted in downregulation of AMBRA1, loricrin and claudin-1, while knockdown of AMBRA1 was associated with decreased expression of claudin-1 and increased proliferation of keratinocytes (P < 0·05). Importantly, we show loss of AMBRA1 in the peritumoral epidermis was associated with decreased claudin-1 expression (P < 0·05), parakeratosis (P < 0·01) and cleft formation in the dermoepidermal junction (P < 0·05).

conclusionsCollectively, these data suggest a paracrine mechanism whereby TGF-β2 causes loss of AMBRA1 overlying high-risk AJCC early-stage melanomas and reduced epidermal integrity, thereby facilitating erosion of the epidermis and tumour ulceration.

Indexed as

MelanomaSkin NeoplasmsAdaptor Proteins, Signal TransducingEpidermisHumansTransforming Growth Factor betaTransforming Growth Factor beta2Transforming Growth FactorsAdaptor Proteins, Signal TransducingAMBRA1 protein, humanTGFB2 protein, humanTransforming Growth Factor betaTransforming Growth Factor beta2Transforming Growth Factors

Identifiers

PMID34773645
PMCPMC9546516
OpenAlexW3214383150

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.