Evidence map›Paper›PMID 34477203›Full record

ArticleJournal of cell science2021

Tyrosine kinase-independent actions of DDR2 in tumor cells and cancer-associated fibroblasts influence tumor invasion, migration and metastasis.

Craig E Barcus, Priscilla Y Hwang, Vasilios Morikis, Audrey Brenot, Patrick Pence, Maria Clarke, Gregory D Longmore

Open access · hybridAbstract read
In one paragraph

Article in Journal of cell science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

13 citing papers in PubMed, 22 citations in OpenAlex.

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  7. TME-Related Biomimetic Strategies Against Cancer.International journal of nanomedicine · 2024
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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

7 authors at 2 institutions in 1 country.

Craig E BarcusICCE Institute, Washington University, St Louis, MO 63110, USA.ORCID 0000-0001-9887-0503
Priscilla Y HwangICCE Institute, Washington University, St Louis, MO 63110, USA.
Vasilios MorikisICCE Institute, Washington University, St Louis, MO 63110, USA.
Audrey BrenotICCE Institute, Washington University, St Louis, MO 63110, USA.
Patrick PenceICCE Institute, Washington University, St Louis, MO 63110, USA.
Maria ClarkeICCE Institute, Washington University, St Louis, MO 63110, USA.
Gregory D LongmoreICCE Institute, Washington University, St Louis, MO 63110, USA.ORCID 0000-0001-7568-8151
Washington University in St. Louis · USVirginia Commonwealth University · US

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI AIMEE S JAMES · 2001 to 2026
$128.0M
The Role of Physical Cues in Collective Cell InvasionU54CA210173 · NCI · JOHNS HOPKINS UNIVERSITY · PI WIRTZ, DENIS · 2016 to 2020
$9.9M
MOLECULAR ONCOLOGY TRAINING GRANTT32CA113275 · NCI · WASHINGTON UNIVERSITY · PI Matthew J Walter · 2006 to 2026
$5.7M
Tumor stromal effects of DDR2 in metastasis regulationR01CA223758 · NCI · WASHINGTON UNIVERSITY · PI LONGMORE, GREGORY D. · 2018 to 2022
$1.9M
NOVEL SMALL MOLECULE INHIBITION OF DDR2 TO PREVENT BREAST CANCER METASTASISR01CA196205 · NCI · WASHINGTON UNIVERSITY · PI LONGMORE, GREGORY D. · 2015 to 2019
$1.7M
NCI NIH HHS P30 CA091842NCI NIH HHS R01 CA196205NCI NIH HHS R01 CA223758NCI NIH HHS T32 CA113275NCI NIH HHS U54 CA210173
6 · The paper itself

Abstract

Both tumor cell-intrinsic signals and tumor cell-extrinsic signals from cells within the tumor microenvironment influence tumor cell dissemination and metastasis. The fibrillar collagen receptor tyrosine kinase (RTK) discoidin domain receptor 2 (DDR2) is essential for breast cancer metastasis in mouse models, and high expression of DDR2 in tumor and tumor stromal cells is strongly associated with poorer clinical outcomes. DDR2 tyrosine kinase activity has been hypothesized to be required for the metastatic activity of DDR2; however, inhibition of DDR2 tyrosine kinase activity, along with that of other RTKs, has failed to provide clinically relevant responses in metastatic patients. Here, we show that tyrosine kinase activity-independent action of DDR2 in tumor cells can support Matrigel invasion and in vivo metastasis. Paracrine actions of DDR2 in tumor cells and cancer-associated fibroblasts (CAFs) also support tumor invasion, migration and lung colonization in vivo. These data suggest that tyrosine kinase-independent functions of DDR2 could explain failures of tyrosine kinase inhibitor treatment in metastatic breast cancer patients and highlight the need for alternative therapeutic strategies that inhibit both tyrosine kinase-dependent and -independent actions of RTKs in the treatment of breast cancer. This article has an associated First Person interview with the first author of the paper.

Indexed as

Breast NeoplasmsCancer-Associated FibroblastsDiscoidin Domain Receptor 2AnimalsCell MovementFemaleFibroblastsHumansMicePhosphorylationTumor MicroenvironmentDDR2 protein, humanDiscoidin Domain Receptor 2Cancer-associated fibroblastsDDR2Kinase independentMetastasisParacrine actions

Identifiers

PMID34477203
PMCPMC8542384
OpenAlexW3197479420

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.