Evidence map›Paper›PMID 33298946›Full record

ArticleNature communications2020

HIF1A signaling selectively supports proliferation of breast cancer in the brain.

Richard Y Ebright, Marcus A Zachariah, Douglas S Micalizzi, Ben S Wittner, Kira L Niederhoffer, Linda T Nieman, Brian Chirn, Devon F Wiley, Benjamin Wesley, Brian Shaw and 9 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
8.4field-weighted citation impact, top 2% 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

56 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.

  1. Pooled it
  2. Review
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  11. CDKN1B (p27/kip1) enhances drug-tolerant persister CTCs by restricting polyploidy following mitotic inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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  18. Mouse Models of Metastasis and Dormancy.Cold Spring Harbor perspectives in medicine · 2024
    Review
  19. Article
  20. 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

19 authors at 3 institutions in 1 country.

Richard Y EbrightMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.ORCID 0000-0001-8975-5810
Marcus A ZachariahMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.
Douglas S MicalizziMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.ORCID 0000-0002-0306-9914
Ben S WittnerMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.ORCID 0000-0001-5657-9849
Kira L NiederhofferMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.
Linda T NiemanMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.
Brian ChirnMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.
Devon F WileyMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.
Benjamin WesleyMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.
Brian ShawMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.
Edwin Nieblas-BedollaMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.
Lian AtlasMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.
Annamaria SzabolcsMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.ORCID 0000-0003-4951-9914
Anthony J IafrateMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.
Mehmet TonerMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.
David T TingMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.ORCID 0000-0002-3261-2322
Priscilla K BrastianosMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.ORCID 0000-0003-4470-8425
Daniel A HaberMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA. dhaber@mgh.harvard.edu.ORCID 0000-0003-1378-6551
Shyamala MaheswaranMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA. maheswaran@helix.mgh.harvard.edu.ORCID 0000-0002-9356-1709
Harvard University · USHoward Hughes Medical Institute · USShriners Hospitals for Children - Erie · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Point-of care Microfluidics for Early Detection of CancerU01EB012493 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI HABER, DANIEL A., TONER, MEHMET · 2010 to 2018
$19.6M
Modeling Metastasis and Acquired Drug Resistance Using Circulating Tumor CellsR01CA129933 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel A. Haber · 2008 to 2026
$7.5M
Identification of genomic drivers of brain metastases in lung adenocarcinomaR01CA227156 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BRASTIANOS, PRISCILLA KALIOPI, CARTER, SCOTT · 2018 to 2022
$3.5M
Using MRI and circulating tumor DNA to improve the interpretation of response to immunotherapy and targeted therapy in CNS metastasesR01CA244975 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BRASTIANOS, PRISCILLA KALIOPI, GERSTNER, ELIZABETH · 2020 to 2024
$3.4M
Metastasis and biophysics of clusters of circulating tumor cells in the microcirculationU01CA214297 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI HABER, DANIEL A., MAHESWARAN, SHYAMALA · 2018 to 2022
$2.9M
Identification of genomic drivers of brain metastases in renal cell carcinomaR21CA220253 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BRASTIANOS, PRISCILLA KALIOPI, CARTER, SCOTT · 2018 to 2019
$421k
Genome-scale CRISPR activation screening to identify lung-specific metastatic pathwaysF30CA232407 · NCI · HARVARD MEDICAL SCHOOL · PI EBRIGHT, RICHARD · 2018 to 2020
$118k
Howard Hughes Medical InstituteNCI NIH HHS F30 CA232407NCI NIH HHS R01 CA129933NCI NIH HHS R01 CA227156NCI NIH HHS R01 CA244975NCI NIH HHS R21 CA220253NCI NIH HHS U01 CA214297NIBIB NIH HHS U01 EB012493NIGMS NIH HHS T32 GM007753
6 · The paper itself

Abstract

Blood-borne metastasis to the brain is a major complication of breast cancer, but cellular pathways that enable cancer cells to selectively grow in the brain microenvironment are poorly understood. We find that cultured circulating tumor cells (CTCs), derived from blood samples of women with advanced breast cancer and directly inoculated into the mouse frontal lobe, exhibit striking differences in proliferative potential in the brain. Derivative cell lines generated by serial intracranial injections acquire selectively increased proliferative competency in the brain, with reduced orthotopic tumor growth. Increased Hypoxia Inducible Factor 1A (HIF1A)-associated signaling correlates with enhanced proliferation in the brain, and shRNA-mediated suppression of HIF1A or drug inhibition of HIF-associated glycolytic pathways selectively impairs brain tumor growth while minimally impacting mammary tumor growth. In clinical specimens, brain metastases have elevated HIF1A protein expression, compared with matched primary breast tumors, and in patients with brain metastases, hypoxic signaling within CTCs predicts decreased overall survival. The selective activation of hypoxic signaling by metastatic breast cancer in the brain may have therapeutic implications.

Indexed as

AnimalsBrainBrain NeoplasmsBreast NeoplasmsCell HypoxiaCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansHypoxia-Inducible Factor 1, alpha SubunitMammary Glands, AnimalMetabolomicsMiceNeoplastic Cells, CirculatingRNA-SeqRNA, Small InterferingHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitRNA, Small Interfering

Identifiers

PMID33298946
PMCPMC7725834
OpenAlexW3111751953

What OpenQuestion 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 OpenQuestion graph.