Jill K. Slack-Davis, PhD
Cell-cell signaling in ovarian cancer
Adhesion-dependent signal transduction pathways are critical regulators of cell growth, death and migration. Loss of adhesion-dependent growth control is a hallmark of transformation. Furthermore, adhesion-dependent signaling pathways are critical regulators of cell migration, a key component of metastasis. Work in the Slack-Davis laboratory focuses on establishing complex cell culture and animal model systems of ovarian and endometrial cancer to investigate the role of adhesion-dependent signaling pathways in regulating tumor progression and metastasis.
Ovarian cancer is associated with a poor prognosis largely due to the advanced stage of disease at the time of diagnosis. These advanced stage tumors typically have peritoneal metastases along with ascites fluid accumulation rendering them principally inoperable and unresponsive to current treatment options. Ovarian carcinomas metastasize by attaching to and invading through the mesothelial lining of the peritoneal cavity. The role of adhesion-dependent signaling mechanisms in the regulation of ovarian cancer attachment and invasion is investigated using co-cultures of mesothelial cells and ovarian cancer cell lines.
Endometrial cancer is associated with relatively low mortality but a high morbidity since the majority of cases are treated by hysterectomy. The favorable prognosis of this disease reflects the fact that the majority of endometrial cancers are diagnosed at an early stage and confined to the uterus, making them ideal targets for less radical treatment options. However, insufficient knowledge about the mechanisms that govern endometrial tumorigenesis has prevented the development of such treatments. Mouse models are powerful tools to study the mechanisms governing the initiation and progression of cancer as well as to test novel Therapeutics. Endometrial cancer is associated with a high incidence of loss of function of PTEN, a lipid phosphatase that regulates cell survival, growth and migration. The development of PTEN conditional knockout mice facilitates the generation of endometrial-specific deletion of PTEN thereby enabling the development of a mouse model of endometrial cancer.