Functional characterization of novel tumor suppressor protein Sav1 in cancer cell proliferation and epithelial‐mesenchymal transition

Abstract

Recent genetic screens of fly mutants and molecular analysis have revealed that the Hippo pathway controls both cell proliferation and apoptosis. Also, the Hippo pathway is reported to play a critical role in regulating tumorigenesis and epithelial‐mesenchymal transition (EMT). Specifically, adaptor protein Sav1 is the key component of the Hippo pathway; however its pathophysiological role in human cancer cells remains largely unknown. In this study, we found that ectopic expression of Sav1 induces apoptosis in human cancer cells and inhibits their growth and survival. In contrast, inhibition of Sav1 expression by shRNA failed to promote the human cancer cell proliferation and EMT. Moreover, we found that transcriptional co‐activator YAP and TAZ, the effector proteins of the Hippo pathway, are phosphorylated in Sav1 knockdown cells by similar extent to control cells. Taken together, although Sav1 is an essential component of the Hippo pathway, our results raise the possibility of Sav1‐independent hippo pathway activation in human cancer cells.