Evidence map›Paper›PMID 32681075›Full record

ArticleNature communications2020

AXL confers cell migration and invasion by hijacking a PEAK1-regulated focal adhesion protein network.

Afnan Abu-Thuraia, Marie-Anne Goyette, Jonathan Boulais, Carine Delliaux, Chloé Apcher, Céline Schott, Rony Chidiac, Halil Bagci, Marie-Pier Thibault, Dominique Davidson and 6 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 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

47 citing papers in PubMed, 61 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

16 authors at 5 institutions in 3 countries.

Afnan Abu-ThuraiaMontreal Clinical Research Institute (IRCM), Montréal, QC, H2W 1R7, Canada.
Marie-Anne GoyetteMontreal Clinical Research Institute (IRCM), Montréal, QC, H2W 1R7, Canada.ORCID http://orcid.org/0000-0003-3199-2252
Jonathan BoulaisMontreal Clinical Research Institute (IRCM), Montréal, QC, H2W 1R7, Canada.ORCID http://orcid.org/0000-0003-1848-0068
Carine DelliauxMontreal Clinical Research Institute (IRCM), Montréal, QC, H2W 1R7, Canada.ORCID http://orcid.org/0000-0003-2632-9376
Chloé ApcherMontreal Clinical Research Institute (IRCM), Montréal, QC, H2W 1R7, Canada.ORCID http://orcid.org/0000-0001-7247-3761
Céline SchottMontreal Clinical Research Institute (IRCM), Montréal, QC, H2W 1R7, Canada.
Rony ChidiacDepartment of Pharmacology and Physiology, Université de Montréal, Montréal, QC, H3C 3J7, Canada.ORCID http://orcid.org/0000-0002-3642-0651
Halil BagciMontreal Clinical Research Institute (IRCM), Montréal, QC, H2W 1R7, Canada.ORCID http://orcid.org/0000-0003-2448-820X
Marie-Pier ThibaultMontreal Clinical Research Institute (IRCM), Montréal, QC, H2W 1R7, Canada.ORCID http://orcid.org/0000-0001-5260-8366
Dominique DavidsonMontreal Clinical Research Institute (IRCM), Montréal, QC, H2W 1R7, Canada.
Mathieu FerronMontreal Clinical Research Institute (IRCM), Montréal, QC, H2W 1R7, Canada.ORCID http://orcid.org/0000-0002-5858-2686
André VeilletteMontreal Clinical Research Institute (IRCM), Montréal, QC, H2W 1R7, Canada.ORCID http://orcid.org/0000-0003-1159-4345
Roger J DalyCancer Program, Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia.ORCID http://orcid.org/0000-0002-5739-8027
Anne-Claude GingrasLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, M5G 1X5, Canada.ORCID http://orcid.org/0000-0002-6090-4437
Jean-Philippe GrattonDepartment of Pharmacology and Physiology, Université de Montréal, Montréal, QC, H3C 3J7, Canada.
Jean-François CôtéMontreal Clinical Research Institute (IRCM), Montréal, QC, H2W 1R7, Canada. jean-francois.cote@ircm.qc.ca.ORCID http://orcid.org/0000-0001-7055-2642
Montreal Clinical Research Institute · CAUniversité de Montréal · CAAustralian Regenerative Medicine Institute · AUETH Zurich · CHUniversity of Toronto · CA

Funding

CIHR MOP-142425
6 · The paper itself

Abstract

Aberrant expression of receptor tyrosine kinase AXL is linked to metastasis. AXL can be activated by its ligand GAS6 or by other kinases, but the signaling pathways conferring its metastatic activity are unknown. Here, we define the AXL-regulated phosphoproteome in breast cancer cells. We reveal that AXL stimulates the phosphorylation of a network of focal adhesion (FA) proteins, culminating in faster FA disassembly. Mechanistically, AXL phosphorylates NEDD9, leading to its binding to CRKII which in turn associates with and orchestrates the phosphorylation of the pseudo-kinase PEAK1. We find that PEAK1 is in complex with the tyrosine kinase CSK to mediate the phosphorylation of PAXILLIN. Uncoupling of PEAK1 from AXL signaling decreases metastasis in vivo, but not tumor growth. Our results uncover a contribution of AXL signaling to FA dynamics, reveal a long sought-after mechanism underlying AXL metastatic activity, and identify PEAK1 as a therapeutic target in AXL positive tumors.

Indexed as

Cell MovementAdaptor Proteins, Signal TransducingAxl Receptor Tyrosine KinaseCell Line, TumorFocal AdhesionsHumansNeoplasm InvasivenessNeoplasmsPaxillinPhosphorylationProtein-Tyrosine KinasesProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSignal TransductionAdaptor Proteins, Signal TransducingAXL protein, humanAxl Receptor Tyrosine KinaseNEDD9 protein, humanPaxillinPEAK1 protein, humanProtein-Tyrosine KinasesProto-Oncogene ProteinsPXN protein, humanReceptor Protein-Tyrosine Kinases

Identifiers

PMID32681075
PMCPMC7368075
OpenAlexW3042561762

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.