Evidence map›Paper›PMID 25150980›Full record

ArticleNature cell biology2014

Loss of the Timp gene family is sufficient for the acquisition of the CAF-like cell state.

Masayuki Shimoda, Simona Principe, Hartland W Jackson, Valbona Luga, Hui Fang, Sam D Molyneux, Yang W Shao, Alison Aiken, Paul D Waterhouse, Christina Karamboulas and 8 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature cell biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed
9.1field-weighted citation impact, top 1% 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

110 citing papers in PubMed, 189 citations in OpenAlex.

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  13. Exosomes in metastasis of colorectal cancers: Friends or foes?World journal of gastrointestinal oncology · 2023
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50 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 5 institutions in 3 countries.

Masayuki ShimodaOntario Cancer Institute, University Health Network, Toronto, M5G 2M9, Canada.
Simona PrincipeOntario Cancer Institute, University Health Network, Toronto, M5G 2M9, Canada.
Hartland W JacksonOntario Cancer Institute, University Health Network, Toronto, M5G 2M9, Canada.
Valbona LugaCentre for Systems Biology, Samuel Lunenfeld Research Institute, Toronto, M5G 1X5, Canada.
Hui FangOntario Cancer Institute, University Health Network, Toronto, M5G 2M9, Canada.
Sam D MolyneuxOntario Cancer Institute, University Health Network, Toronto, M5G 2M9, Canada.
Yang W ShaoOntario Cancer Institute, University Health Network, Toronto, M5G 2M9, Canada.
Alison AikenOntario Cancer Institute, University Health Network, Toronto, M5G 2M9, Canada.
Paul D WaterhouseOntario Cancer Institute, University Health Network, Toronto, M5G 2M9, Canada.
Christina KaramboulasOntario Cancer Institute, University Health Network, Toronto, M5G 2M9, Canada.
Franz M HessInstitute of Pharmacology and Toxicology, RWTH Aachen University, 52074 Aachen, Germany.
Takashi OhtsukaKeio University, School of Medicine, Tokyo 160-8582, Japan.
Yasunori OkadaKeio University, School of Medicine, Tokyo 160-8582, Japan.
Laurie AillesOntario Cancer Institute, University Health Network, Toronto, M5G 2M9, Canada.
Andreas LudwigInstitute of Pharmacology and Toxicology, RWTH Aachen University, 52074 Aachen, Germany.
Jeffrey L WranaCentre for Systems Biology, Samuel Lunenfeld Research Institute, Toronto, M5G 1X5, Canada.
Thomas KislingerOntario Cancer Institute, University Health Network, Toronto, M5G 2M9, Canada.
Rama KhokhaOntario Cancer Institute, University Health Network, Toronto, M5G 2M9, Canada.
Ontario Institute for Cancer Research · CAUniversity Health Network · CAKeio University · JPLunenfeld-Tanenbaum Research Institute · CARWTH Aachen University · DE

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Cancer-associated fibroblasts (CAFs) drive tumour progression, but the emergence of this cell state is poorly understood. A broad spectrum of metalloproteinases, controlled by the Timp gene family, influence the tumour microenvironment in human cancers. Here, we generate quadruple TIMP knockout (TIMPless) fibroblasts to unleash metalloproteinase activity within the tumour-stromal compartment and show that complete Timp loss is sufficient for the acquisition of hallmark CAF functions. Exosomes produced by TIMPless fibroblasts induce cancer cell motility and cancer stem cell markers. The proteome of these exosomes is enriched in extracellular matrix proteins and the metalloproteinase ADAM10. Exosomal ADAM10 increases aldehyde dehydrogenase expression in breast cancer cells through Notch receptor activation and enhances motility through the GTPase RhoA. Moreover, ADAM10 knockdown in TIMPless fibroblasts abrogates their CAF function. Importantly, human CAFs secrete ADAM10-rich exosomes that promote cell motility and activate RhoA and Notch signalling in cancer cells. Thus, Timps suppress cancer stroma where activated-fibroblast-secreted exosomes impact tumour progression.

Indexed as

ADAM10 ProteinADAM ProteinsAmyloid Precursor Protein SecretasesAnimalsCell Line, TumorCell MovementExosomesFemaleFibroblastsHumansLung NeoplasmsMammary Neoplasms, ExperimentalMembrane ProteinsMetalloendopeptidasesMiceMice, Inbred C57BLADAM10 ProteinADAM10 protein, humanADAM ProteinsAmyloid Precursor Protein SecretasesMembrane ProteinsMetalloendopeptidasesTissue Inhibitor of Metalloproteinases

Identifiers

PMID25150980
OpenAlexW2022956911

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.