The role of the Hippo pathway effectors YAP and TAZ in liver cancer

Breast cancer remains the second-leading cause of death in women. One of the big issues in breast cancer is that tumor cells can remain in a dormant state for many years before they grow into secondary tumors. Such recurrent cancers are often resistant to chemotherapy, resulting in poor prognosis. Our objectives are to understand the molecular mechanisms that drive cancer cells into dormancy, that maintain cancer in dormancy and that trigger exit from dormancy. Based on preliminary findings, we hypothesize that cancer cells enter dormancy by inactivating two specific proteins, known as Yap and Taz. Yap and Taz are known cancer genes and they are abnormally activated in multiple types of cancer. In addition, we found striking difference in the regulation of Yap and Taz between ER+ and ER- cancer cells that we think may explain why ER- breast cancers are more aggressive and resistant to chemotherapy. Our aim is to determine the role of Yap/Taz in breast cancer cell dormancy. We hypothesize that ER+ and ER- breast cancer cells differ in their aggressiveness and potential to enter dormancy because they have differences in Yap/Taz activity and regulation. We also aim to determine the mechanism of Yap/Taz regulation by mechanical forces and during cancer cell dormancy. For our studies, we will use new cell culture models that more closely mimic in vivo situations and for the first time provide experimental models to study cancer cell dormancy. We expect that the proposed research will provide fundamental new insights into cancer cell dormancy, a clinically highly relevant cancer mechanism. It is our goal to deliver conceptual advances in a highly significant area of cancer research

Publication year:2019

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