Evidence map›Paper›PMID 22553342›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012

Role of Apollon in human melanoma resistance to antitumor agents that activate the intrinsic or the extrinsic apoptosis pathways.

Elena Tassi, Marina Zanon, Claudia Vegetti, Alessandra Molla, Ilaria Bersani, Valentina Perotti, Marzia Pennati, Nadia Zaffaroni, Michele Milella, Soldano Ferrone and 4 more

Open access · greenAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

19 citing papers in PubMed, 28 citations in OpenAlex.

  1. TheInternational journal of molecular sciences · 2021
    Trial
  2. The IAP family member BRUCE/BIRC6: an emerging new player in balancing life and death.Apoptosis : an international journal on programmed cell death · 2026
    Review
  3. Article
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  8. Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs).Apoptosis : an international journal on programmed cell death · 2017
    Review
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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

14 authors at 2 institutions in 2 countries.

Elena TassiHuman Tumors Immunobiology Unit, Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Medical Oncology Unit 3, Department of Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Italy.
Marina Zanon
Claudia Vegetti
Alessandra Molla
Ilaria Bersani
Valentina Perotti
Marzia Pennati
Nadia Zaffaroni
Michele Milella
Soldano Ferrone
Carmelo Carlo-Stella
Alessandro M Gianni
Roberta Mortarini
Andrea Anichini
UPMC Hillman Cancer Center · USFondazione IRCCS Istituto Nazionale dei Tumori · IT

Funding

Tissue Procurement / ImmunohistologyP01CA109688 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SCHLESSELMAN, JAMES J · 2006 to 2010
$5.9M
Combinatorial targeting of melanoma initiating cellsR01CA138188 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FERRONE, SOLDANO · 2008 to 2012
$1.5M
Antigen processing and HLA-peptide complexes in head and neck cancerR01CA110249 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FERRONE, SOLDANO · 2006 to 2010
$1.5M
NCI NIH HHS P01 CA109688NCI NIH HHS R01 CA110249NCI NIH HHS R01 CA113369NCI NIH HHS R01 CA138188
6 · The paper itself

Abstract

purposeTo assess the role of Apollon in melanoma resistance to intrinsic and extrinsic pathways of apoptosis and to identify strategies to reduce its expression. EXPERIMENTAL

designApollon expression was assessed in melanoma cells in vitro and in vivo. Apollon modulation and melanoma apoptosis were evaluated by Western blot and/or flow cytometry in response to cytotoxic drugs, mitogen-activated protein/extracellular signal-regulated kinase (MEK)-, BRAF(V600E)-, and mTOR-specific inhibitors, TRAIL and anti-HLA class II monoclonal antibodies (mAb). Mitochondrial depolarization, caspase activation, apoptosis assays, and gene expression profiling were used to test effects of Apollon silencing, by siRNA, on melanoma response to antitumor agents.

resultsApollon was constitutively expressed by melanoma cells, in vitro and in vivo, and at higher levels than in benign melanocytic lesions. Melanoma apoptosis correlated significantly with Apollon protein downmodulation in response to cytotoxic drugs, MEK, or BRAF(V600E)-specific inhibitors. Combinatorial treatment with MEK and mTOR inhibitors and HLA class II ligation, by a specific mAb, promoted Apollon downmodulation and enhanced melanoma apoptosis. Apollon downmodulation induced by antitumor agents was caspase independent, but proteasome dependent. Knockdown of Apollon, by siRNA, triggered apoptosis and/or significantly enhanced melanoma cell death in response to cytotoxic drugs, MEK- and BRAF(V600E)-specific inhibitors, and soluble or membrane-bound TRAIL. Apollon silencing promoted mitochondrial depolarization and caspase-2, caspase-8, caspase-9, and caspase-3 activation in response to different antitumor agents and altered the profile of genes modulated by MEK or BRAF(V600E)-specific inhibitors.

conclusionsTargeting of Apollon may significantly improve melanoma cell death in response to antitumor agents that trigger the intrinsic or the extrinsic apoptosis pathways.

Indexed as

Antibodies, MonoclonalAntineoplastic AgentsApoptosisCaspase 2Caspase 3Caspase 8Caspase 9Cell Line, TransformedCell PolarityDown-RegulationEnzyme ActivationExtracellular Signal-Regulated MAP KinasesGene Expression ProfilingHumansInhibitor of Apoptosis ProteinsMelanomaAntibodies, MonoclonalAntineoplastic AgentsBIRC6 protein, humanBRAF protein, humanCaspase 2Caspase 3Caspase 8Caspase 9Extracellular Signal-Regulated MAP KinasesInhibitor of Apoptosis ProteinsMTOR protein, humanProto-Oncogene Proteins B-rafRNA, Small InterferingTOR Serine-Threonine Kinases

Identifiers

PMID22553342
PMCPMC3426233
OpenAlexW1993597680

What OpenQuestion 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 OpenQuestion graph.