We welcome our next speaker for our seminar series, Dr. Danijela Vignjevic. She is the team leader for the Cell Migration and Invasion team within the Cell Biology and Cancer Department at the Institut Curie.
Cancer-associated Fibroblasts Form Contractile Intratumoral Capsules that Actively Compress Cancer Cells and Modulate Mechanotransduction
ABSTRACT: During tumor progression, cancer-associated fibroblasts (CAFs) accumulate in tumors and produce exces- sive extracellular matrix (ECM), forming a capsule that enwraps cancer cells. This capsule is a barrier that restricts tumor growth leading to the buildup of intratumoral pressure. Combining genetic and physical ma- nipulations in vivo with microfabrication and force measurements in vitro, we found that the CAFs capsule is not a passive barrier but instead actively compresses cancer cells using actomyosin contractility. Cancer cells mechanosense CAF compression, resulting in an altered localization of the transcriptional regulator YAP. Abrogation of CAFs contractility in vivo leads to the dissipation of compressive forces and impairment of capsule formation. By mapping CAF force patterns in 3D, we show that compression is a CAF-intrinsic prop- erty independent of cancer cell growth. Supracellular coordination of CAFs is achieved through fibronectin cables that serve as scaffolds allowing force transmission. Our study unveils that the contractile capsule actively compresses cancer cells, modulates their mechanical signaling, and reorganizes tumor morphology. Please find attached the Biodata.
BIO: Danijela Matic Vignjevic was trained as a molecular biologist at the University of Belgrade, Serbia, and University of Wisconsin-Madison, US. She did her Ph.D. in cell biology, working on the role of the actin cytoskeleton in cell migration in the lab of Gary Borisy at Northwestern University, Chicago, US. She then did a post-doc in the lab of Daniel Louvard at Institut Curie, working on mouse models for colon cancer metastasis as a HFSP fellow. After being recruited as an INSERM researcher, she continued working on cell migration-related questions. She started her independent team in 2013 when she got interested in how epithelial cells interact with their microenvironment (focusing on ECM and fibroblasts) in homeostasis and during cancer invasion. Her research strategy combines molecular and cell biology techniques with live-cell imaging using different model systems such as 2D and 3D in vitro cell cultures, tissue slices cultured ex vivo, and different transgenic mouse models. She is the recipient of ERC Starting grant (2013-2017) and Consolidator grant (2018-2023), and she received several awards such as “Grand Prix” in Cancer research, Foundation Simone et Cino del Luca, and Dandrimont-Benicourt, French Academy of Science.
