The Extracellular Matrix of Tumors: A Focus on Fibronectin and Fibulin-5
The extracellular matrix (ECM) in tumors is highly dynamic and contributes to tumor evolution. Fibronectin (FN) is a key component of the ECM in tumors that ligates and stimulates integrins on tumor cells, fibroblasts and endothelial cells in the tumor microenvironment. FN induced integrin activity is reduced by fibulin-5 (Fbln5), a matricellular protein that competes with FN for integrin binding but does not stimulate integrin signaling. A consequence of FN-induced integrin activation is the generation of reactive oxygen species (ROS), which can promote cell survival or apoptosis pending the microenvironment. The tumor microenvironment Fbln5 can be viewed as a molecular rheostat that tunes FN stimulated integrin-induced ROS generation.
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