Abstract POSTER-BIOL-1302: Sucrose nonfermenting 1-related kinase (SNRK) expression and function in vitro in ovarian cancer cells

Abstract

Abstract Purpose of study: Lipid metabolism and transport have recently been identified as potential targets for the treatment of cancers where adipocytes are a major component of the tumor microenvironment. Ovarian cancer metastases have a clear predilection for the omentum, which is primarily comprised of adipocytes. Studies have shown that human omental adipocytes promote migration and invasion of ovarian cancer cells and that adipocyte–ovarian cancer cell coculture promotes tumor growth and induces lipolysis in adipocytes and β-oxidation in cancer cells. SNRK is a serine/threonine kinase with sequence similarity to AMP-activated protein kinase (AMPK). AMPK proteins play a central role in cellular energy regulation. Active AMPK restricts cell proliferation, cell growth, and metabolic substrate synthesis, and increases ATP-generating processes, such as glucose and fatty acid oxidation. It has also been suggested that SNRK suppresses adipocyte inflammation via mTORC1 which is a pathway known to be aberrant in ovarian cancer. SNRK has been shown to reduce colon cancer cell proliferation and DNA synthesis and SNRK levels are decreased in human colon cancer tissue. Stable knockdown of SNRK increases in vitro colon cancer cell tumorigenicity indicating that SNRK is a regulator of cell proliferation. Because of the role SNRK appears to play in cell proliferation and metabolism and the link between SNRK and mTORC1 signaling, the goal of this study is to describe expression of SNRK in ovarian cancer cell lines and ovarian tissue from mice. Experimental Procedures: The ovarian cancer cell lines A2780 and SKOV3ip1 as well as a normal surface epithelial cell line IOSE, were grown in culture media and then immunostained for SNRK, as well as CC3 (apoptosis) and PH3 (proliferation). To assess the expression of SNRK in mice, ovarian tissue from wild type mice were harvested and immunostained for SNRK. Summary of data: Cell line immunostaining demonstrated differential expression of SNRK in both ovarian cancer cell lines and the benign ovarian epithelial cell line along with PH3 staining. There was no CC3 staining seen in any of the cell lines. The mouse ovarian tissue shows SNRK staining in the nuclei of follicular cells but no clear staining in the epithelial or stromal cells. Conclusions: Our results show the presence of SNRK in both benign and malignant epithelial ovarian cell lines as well as in benign mouse ovarian tissue. We plan to further explore SNRK expression levels in ovarian cancer by quantifying SNRK mRNA and protein levels in ovarian cancer cell lines as well as in human benign and malignant ovarian tissue. We also plan to knockdown SNRK expression in ovarian cancer cell lines to determine effects on cell proliferation, migration, and invasion as well as changes in proteins involved in proliferation and metabolism. Citation Format: Erin Bishop, Stephanie Cossette, Vakeel Padmanabhan, Ramani Ramchandran. Sucrose nonfermenting 1-related kinase (SNRK) expression and function in vitro in ovarian cancer cells [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-BIOL-1302.