For example, in response to increased ECM rigidity, the SH2 domain of TNS1 binds to tyrosine-phosphorylated Hic-5 and elicits a mechano-transduction that leads to the activation of the Rho/ROCK signaling pathway and fiber formation in tumor-associated fibroblasts, which in turn increases ECM stiffness and promotes tumor cell proliferation, invasion, and metastasis [76]. This evidence concerns the gene RHO and neoplasm.