Evidence map›Paper›PMID 36001971›Full record

ArticleCell reports2022

Pituitary adenomas evade apoptosis via noxa deregulation in Cushing's disease.

David T Asuzu, Reinier Alvarez, Patrick A Fletcher, Debjani Mandal, Kory Johnson, Weiwei Wu, Abdel Elkahloun, Paul Clavijo, Clint Allen, Dragan Maric and 9 more

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

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

17 citing papers in PubMed, 33 citations in OpenAlex.

  1. Phosphoproteomic dysregulation promotes tumor proliferation in Cushing's disease.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. DNA Methylation in Pituitary Adenomas: A Scoping Review.International journal of molecular sciences · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. scRNA sequencing technology for PitNET studies.Frontiers in endocrinology · 2024
    Review
  14. Review
  15. Article
  16. Article
  17. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 7 institutions in 1 country.

David T AsuzuNeurosurgery Unit for Pituitary and Inheritable Diseases, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, Room 3D20, Bethesda, MD 20892, USA; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA; Department of Neurosurgery, University of Virginia, Charlottesville, VA, USA.
Reinier AlvarezNeurosurgery Unit for Pituitary and Inheritable Diseases, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, Room 3D20, Bethesda, MD 20892, USA; Florida International University Herbert Wertheim College of Medicine, Miami, FL, USA.
Patrick A FletcherLaboratory of Biological Modeling, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD, USA.
Debjani MandalNeurosurgery Unit for Pituitary and Inheritable Diseases, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, Room 3D20, Bethesda, MD 20892, USA.
Kory JohnsonDIR Bioinformatics Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
Weiwei WuCancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, Bethesda, MD, USA.
Abdel ElkahlounCancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, Bethesda, MD, USA.
Paul ClavijoTranslational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, Bethesda, MD, USA.
Clint AllenTranslational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, Bethesda, MD, USA.
Dragan MaricFlow and Imaging Cytometry Core Facility, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
Abhik Ray-ChaudhurySurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA; Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Sharika RajanLaboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Zied AbdullaevLaboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Diana NwokoyeNeurosurgery Unit for Pituitary and Inheritable Diseases, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, Room 3D20, Bethesda, MD 20892, USA.
Kenneth AldapeLaboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Lynnette K NiemanSection on Translational Endocrinology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.
Constantine StratakisSection on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA.
Stanko S StojilkovicSection on Cellular Signaling, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA.
Prashant ChittiboinaNeurosurgery Unit for Pituitary and Inheritable Diseases, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, Room 3D20, Bethesda, MD 20892, USA; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA. Electronic address: prashant.chittiboina@nih.gov.
National Institutes of Health · USNational Cancer Institute · USNational Institute of Neurological Disorders and Stroke · USEunice Kennedy Shriver National Institute of Child Health and Human Development · USNational Human Genome Research Institute · USNational Institute of Diabetes and Digestive and Kidney Diseases · USNational Institute on Deafness and Other Communication Disorders · US

Funding

Intracellular Signaling In Endocrine CellsZIAHD000195 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI STOJILKOVIC, STANKO S. · 2009 to 2025
$18.8M
Neuro-oncology of Familial Neoplasia SyndromesZIANS003053 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI CHITTIBOINA, PRASHANT · 2009 to 2025
$14.9M
Improved Diagnosis and Treatment of Cushing's DiseaseZIANS003150 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI CHITTIBOINA, PRASHANT · 2015 to 2025
$13.7M
Neurooncology of Benign Central and Peripheral Nervous System TumorsZIANS003132 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI CHITTIBOINA, PRASHANT · 2012 to 2025
$7.8M
The differential diagnosis and treatment of Cushing's syndromeZIADK075122 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI NIEMAN, LYNNETTE · 2016 to 2025
$4.0M
The Physiology Of HypercortisolismZIADK075121 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI NIEMAN, LYNNETTE · 2016 to 2024
$1.7M
Intramural NIH HHS ZIA NS003150
6 · The paper itself

Abstract

Sporadic pituitary adenomas occur in over 10% of the population. Hormone-secreting adenomas, including those causing Cushing's disease (CD), cause severe morbidity and early mortality. Mechanistic studies of CD are hindered by a lack of in vitro models and control normal human pituitary glands. Here, we surgically annotate adenomas and adjacent normal glands in 25 of 34 patients. Using single-cell RNA sequencing (RNA-seq) analysis of 27594 cells, we identify CD adenoma transcriptomic signatures compared with adjacent normal cells, with validation by bulk RNA-seq, DNA methylation, qRT-PCR, and immunohistochemistry. CD adenoma cells include a subpopulation of proliferating, terminally differentiated corticotrophs. In CD adenomas, we find recurrent promoter hypomethylation and transcriptional upregulation of PMAIP1 (encoding pro-apoptotic BH3-only bcl-2 protein noxa) but paradoxical noxa downregulation. Using primary CD adenoma cell cultures and a corticotroph-enriched mouse cell line, we find that selective proteasomal inhibition with bortezomib stabilizes noxa and induces apoptosis, indicating its utility as an anti-tumor agent.

Indexed as

AdenomaPituitary ACTH HypersecretionPituitary NeoplasmsAdrenocorticotropic HormoneAnimalsApoptosisHumansMiceAdrenocorticotropic HormonebortezomibCP: CancerCP: Molecular biologyCushing’s diseaseDNA methylationpreclinical testingproteasomesingle-cell RNA-seqsporadic pituitary adenoma

Identifiers

PMID36001971
PMCPMC9527711
OpenAlexW4292755703

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.