Activating the Hippo molecular signaling pathway in liver tumor cells drives tumor growth--but activating the same pathway in healthy cells surrounding the tumor suppresses tumor growth. This unexpected effect indicates that there is a competitive interaction between tumor cells and their surrounding tissues, say Iván Moya and colleagues. The Hippo pathway and in particular two of its components, the transcriptional coactivators Yap and Taz, have been identified in experimental studies as drivers of tumor growth, making it a potential target in cancer treatments. However, the new findings by Moya et al. suggest that systemic inhibition of Yap and Taz could have unwanted consequences, by blocking the tumor-suppressing abilities of healthy cells at the tumor margin. In a mouse model of liver cancer, the researchers found Yap and Taz activity in the cells surrounding a tumor prompted cell death in the tumor cells. They also confirmed that while liver tumor cells rely on Yap and Taz for their survival, this effect is relative to the levels of Yap and Taz in surrounding cells. When Yap and Taz activity is higher in surrounding cells relative to the tumor cells, the tumors shrink--but can rebound when Yap and Taz activity is neutralized in surrounding cells.
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Journal
Science