For instance, exposing adipose stromal cells to breast cancer-cell secreted factors leads to the deposition of a high amount of stiff and unfolded FN.222 The conformational changes of tumor-associated FN increase the spatial separation between the integrin-binding sequence of FN (FNIII9–FNIII10), forcing cells to switch from α5β1 to αvβ3 binding, which is insensitive to the increased distance between FNIII9 and FNIII10. This evidence concerns the gene FN1 and breast cancer.