Abstract

Tissue homeostasis is dependent on the spatially controlled localization of specific cell types and the correct composition of the extracellular stroma. Integrin mediated adhesions, in conjunction with the actin cytoskeleton, allow cells to sense the stiffness of the surrounding extra-cellular matrix (ECM). Conversely, cells exert acto-myosin and integrin dependent forces to remodel and organize the surrounding ECM . In cancer, stiffening of the tumor stroma is considered as an instrumental contributor to tumor progression. However, the mechanisms how the stromal ECM regulates cancer progression is not fully understood. I will describe our recent findings on the interrelationship between cancer cell mediated ECM remodelling and ECM induced mechanochemical signals regulating transcription of growth promoting pathways in cancer cells. Endosomal trafficking of integrins and receptor tyrosine kinases (RTK) is a central mechanism for regulating their cell surface availability and downstream signaling. Co-endocytosis of integrins and RTKs and endosomal cross-talk between these receptors is implicated in oncogenic transformation. I will describe our recent observations for endosomal signalling driving breast cancer tumorigenic properties.