To address this unresolved question, the present work demonstrates that the binding of α2β1 integrin to collagen IV, which is the ECM that is highly accumulated in tumor interstitium [45, 46], inhibits the Hippo core kinases MST1 and LATS1, liberating YAP for its transactivation of gene expression in the nucleus (Figure 6). This evidence concerns the gene YAP1 and neoplasm.