Based on our accumulated in vitro data, we propose that Hsp27 overexpression in cancer cells inactivates the Hippo tumor suppressor pathway by potentiating MST1 degradation, resulting in the disruption of the Hippo kinase cascade, decreased YAP phosphorylation, and ultimately increased YAP/TAZ nuclear localization that drives transcription of genes associated with malignant cell phenotypes (Fig. 6). The gene discussed is YAP1; the disease is cancer.