DDR2 controls breast tumor stiffness and metastasis by regulating integrin mediated mechanotransduction in CAFs.
DDR2
Integrins
cancer biology
cell biology
collagen
mechanotransduction
metastasis
mouse
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
30 05 2019
30 05 2019
Historique:
received:
24
01
2019
accepted:
29
05
2019
pubmed:
31
5
2019
medline:
26
2
2020
entrez:
31
5
2019
Statut:
epublish
Résumé
Biomechanical changes in the tumor microenvironment influence tumor progression and metastases. Collagen content and fiber organization within the tumor stroma are major contributors to biomechanical changes (e., tumor stiffness) and correlated with tumor aggressiveness and outcome. What signals and in what cells control collagen organization within the tumors, and how, is not fully understood. We show in mouse breast tumors that the action of the collagen receptor DDR2 in CAFs controls tumor stiffness by reorganizing collagen fibers specifically at the tumor-stromal boundary. These changes were associated with lung metastases. The action of DDR2 in mouse and human CAFs, and tumors in vivo, was found to influence mechanotransduction by controlling full collagen-binding integrin activation via Rap1-mediated Talin1 and Kindlin2 recruitment. The action of DDR2 in tumor CAFs is thus critical for remodeling collagen fibers at the tumor-stromal boundary to generate a physically permissive tumor microenvironment for tumor cell invasion and metastases.
Identifiants
pubmed: 31144616
doi: 10.7554/eLife.45508
pii: 45508
pmc: PMC6555593
doi:
pii:
Substances chimiques
Integrins
0
Collagen
9007-34-5
DDR2 protein, human
EC 2.7.10.1
Ddr2 protein, mouse
EC 2.7.10.1
Discoidin Domain Receptor 2
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : T32 CA113275
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA210173
Pays : United States
Organisme : NCI NIH HHS
ID : F30 CA200386
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA223758
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007200
Pays : United States
Organisme : American Cancer Society
ID : 131342-PF-17-238-01-CSM
Pays : International
Organisme : National Institute for Health Research
ID : T32 GM07200
Pays : International
Organisme : NCI NIH HHS
ID : R01 CA196205
Pays : United States
Informations de copyright
© 2019, Bayer et al.
Déclaration de conflit d'intérêts
SB, WG, AB, PH, CB, ME, PP, CW, AP, GL No competing interests declared
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