@article{25c7ed3780904244853c796c8d9d3d4b,
title = "DDR2 controls breast tumor stiffness and metastasis by regulating integrin mediated mechanotransduction in cafs",
abstract = "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.",
author = "Bayer, {Samantha Vh} and Grither, {Whitney R.} and Audrey Brenot and Hwang, {Priscilla Y.} and Barcus, {Craig E.} and Melanie Ernst and Patrick Pence and Christopher Walter and Amit Pathak and Longmore, {Gregory D.}",
note = "Funding Information: This work was supported by NIH grants R01 CA196205, R01 CA223758, and U54 CA210173 (GDL), F30 CA200386 (SVHB), T32 GM07200 (WRG), and T32 CA113275 (CEB). PYH was supported by an American Cancer Society Postdoctoral Fellowship, and a WM Keck Foundation Postdoctoral Fellowship. We also gratefully acknowledge assistance in imaging provided the Washington University Center for Cellular Imaging (WUCCI), which is supported by Washington University School of Medicine, The Children{\textquoteright}s Discovery Institute of Washington University and St Louis Children{\textquoteright}s Hospital (CDI-CORE-2015–505) and the Foundation for Barnes-Jewish Hospital (3770). Funding Information: This work was supported by NIH grants R01 CA196205, R01 CA223758, and U54 CA210173 (GDL), F30 CA200386 (SVHB), T32 GM07200 (WRG), and T32 CA113275 (CEB). PYH was supported by an American Cancer Society Postdoctoral Fellowship, and a WM Keck Foundation Postdoctoral Fellow-ship. We also gratefully acknowledge assistance in imaging provided the Washington University Center for Cellular Imaging (WUCCI), which is supported by Washington University School of Mediine, The Children?s Discovery Institute of Washington University and St Louis Children?s Hospital (CDI-CORE-2015?505) and the Foundation for Barnes-Jewish Hospital (3770). National Institute for Health Research R01 CA196205 National Institute for Health Research R01 CA223758 National Institute for Health Research U54 CA210173 American Cancer Society 131342-PF-17-238-01-CSM National Institute for Health Research F30 CA200386 National Institute for Health Research T32 GM07200 National Institute for Health Research T32 CA113275 Publisher Copyright: {\textcopyright} Bayer et al.",
year = "2019",
month = may,
doi = "10.7554/eLife.45508",
language = "English",
volume = "8",
journal = "eLife",
issn = "2050-084X",
}