Evidence map›Paper›PMID 36973439›Full record

ArticleNature cancer2023

Apoptosis-induced nuclear expulsion in tumor cells drives S100a4-mediated metastatic outgrowth through the RAGE pathway.

Woo-Yong Park, Justin M Gray, Ronald J Holewinski, Thorkell Andresson, Jae Young So, Carmelo Carmona-Rivera, M Christine Hollander, Howard H Yang, Maxwell Lee, Mariana J Kaplan and 2 more

Open access · hybridFull text read
In one paragraph

Article in Nature cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
8.5field-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

36 citing papers in PubMed, 55 citations in OpenAlex.

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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

12 authors at 1 institution in 1 country.

Woo-Yong Park *Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Justin M Gray *Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Ronald J HolewinskiProtein Mass Spectrometry Group, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Thorkell AndressonProtein Mass Spectrometry Group, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Jae Young SoLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Carmelo Carmona-RiveraSystemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-7706-1464
M Christine HollanderLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Howard H YangLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Maxwell LeeLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-3738-1292
Mariana J KaplanSystemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Steven D CappellLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-2885-7327
Li YangLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. yangl3@mail.nih.gov.ORCID http://orcid.org/0000-0002-0930-206X
National Institutes of Health · US

Funding

Systemic AutoimmunityZIAAR041199 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI KAPLAN, MARIANA · 2014 to 2025
$32.5M
Myeloid TGFbeta signaling in breast cancer metastasis and dormancyZIABC011163 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI YANG, LI · 2009 to 2025
$14.5M
Study cell cycle regulation in dormant tumor cellsZIABC011832 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI CAPPELL, STEVEN · 2018 to 2025
$4.7M
6 · The paper itself

Abstract

Most tumor cells undergo apoptosis in circulation and at the metastatic organ sites due to host immune surveillance and a hostile microenvironment. It remains to be elucidated whether dying tumor cells have a direct effect on live tumor cells during the metastatic process and what the underlying mechanisms are. Here we report that apoptotic cancer cells enhance the metastatic outgrowth of surviving cells through Padi4-mediated nuclear expulsion. Tumor cell nuclear expulsion results in an extracellular DNA-protein complex that is enriched with receptor for advanced glycation endproducts (RAGE) ligands. The chromatin-bound RAGE ligand S100a4 activates RAGE receptors in neighboring surviving tumor cells, leading to Erk activation. In addition, we identified nuclear expulsion products in human patients with breast, bladder and lung cancer and a nuclear expulsion signature correlated with poor prognosis. Collectively, our study demonstrates how apoptotic cell death can enhance the metastatic outgrowth of neighboring live tumor cells.

Indexed as

Lung NeoplasmsS100 Calcium-Binding Protein A4ApoptosisHumansReceptor for Advanced Glycation End ProductsTumor MicroenvironmentReceptor for Advanced Glycation End ProductsS100A4 protein, humanS100 Calcium-Binding Protein A4

Identifiers

PMID36973439
PMCPMC10042736
OpenAlexW4360991066

What OpenQuestion holds

Textfull text, public
LicenceCC BY
reference markers read1
measurements read117
identifiers read1
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.