A pinboard by
Atefeh Abedini

Post doc, Ottawa hospital research Ins. (OHRI)


Epithelial Ovarian Cancers (EOC) have been reported to arise mainly from the epithelia of the ovarian surface (OSE) and distal fallopian tube. However, the molecular mechanisms underlying the initiation and progression of EOC derived from the OSE remains unclear. The Hippo singling pathway controls organ size and tumorigenesis through a kinase cascade that inactivates YAP protein. Unphosphorylated YAP activates genes involved in cell proliferation and survival, and YAP activation is suppressed by large tumor suppressor family (LATS1 and 2) members. It has been shown that LATS1 is expressed in human ovarian epithelium, but this expression is decreased in the transition to carcinoma, although the role of LATS1 during this process is unknown. In this study, our objective was to explore the consequences of loss of LATS1/2 in OSE cells. OSE cell-specific deletion of Lats1/2 in the mouse ovaries. Our results indicated that ovarian tumors were detected in all injected animals (n=10) after a month. Mice subjected to injection exhibited the tumor in their ovaries and all animals had ascites with metastases spread throughout the peritoneal cavity. Histologically, these tumors derived from the conditional deletion of Lats1/2 resembled high-grade serous carcinoma (HGSC) that is the most aggressive type of human ovarian cancer. Moreover, we found a drug that can use to inhibit tumor growth derived from these mice. Collectively, the data indicate that dysregulation of the Hippo signaling pathway can lead to the initiation and progression of ovarian cancer and loss of LATS1/2 is a potent stimulus for the growth of ovarian serous carcinoma.