FN1 and cancer: In contrast, αvβ3 integrins require only the RGD site, i.e., weaker αvβ3-Fn binding is conformation-independent and occurs even when Fn is unfolded during ECM remodeling.28 Weak Fn-αvβ3 adhesions131 by cancer cells then lead to greater cytoskeletal reorganization for enhanced migration capacity9 and resistance against anoikis (Fig. 1b).170 Once Fn conformation is altered during tumorigenesis, cell–matrix interactions are dysregulated and changes to downstream signaling take place.