Abstract 1251: Potential tumor suppressor function of polo-like kinase 5 in ovarian cancers

Abstract

Abstract Ovarian cancer remains one of the leading causes of cancer-related deaths in women worldwide, with an estimated 295,414 new cases and 184,799 deaths to occur in 2018. In the United States, although this malignancy is not in the top 10 for number of estimated new cases, it is the 5th leading cause of cancer-related deaths in women. This disparity is due to the fact that most ovarian cancers are not diagnosed until late stages when only limited options for treatment are available. Therefore, it is important to uncover novel molecular mechanisms that can be targeted to control this deadly cancer. The polo-like kinases (PLKs 1-5) are a family of serine/threonine kinases that that primarily play key roles in cell cycle progression, and have been linked to cancer pathogenesis. Limited information is available regarding the role of PLK5 in cancer. PLK5 is structurally unique, in that it has been shown to be missing the majority of the kinase domain that the other family members have. Interestingly, although PLK5 is not expressed in many tissues, it has been found to be present in appreciable levels in fallopian tube tissue, which suggests that PLK5 may be important in fallopian tube biology. Contrary to previous dogma, recent research has suggested that most ovarian cancers may actually have their origin in the fallopian tubes. Keeping this in mind, we wanted to explore the role of PLK5 in fallopian cancer. To this end, we performed a quantitative immunostaining of PLK5 in a fallopian tube disease tissue microarray (TMA) containing 5 normal tissues, 10 cases of inflammation, 10 fallopian adenocarcinoma, and 4 adjacent normal tissues. Following staining, the TMA was scanned with the Vectra platform and immunostaining was analyzed using InForm software that allows us to quantitatively measure the PLK5 intensity in each tissue and subcellular compartment. Our data demonstrated that PLK5 protein levels were significantly decreased in fallopian tumors compared to normal fallopian tissue (p = 0.01). Interestingly, although there was no significant difference between inflamed tissue and normal tissue, PLK5 levels were significantly reduced in the fallopian tube adenocarcinomas compared to the inflamed fallopian tissue (p<0.001), suggesting a potential role for PLK5 in fallopian tube carcinogenesis. Further, our data demonstrated that PLK5 was enriched in the nucleus (p<0.001) versus the cytoplasm, which is the opposite of what has been previously published in human neurons and glial cells. Taken together, our data suggests that PLK5 may be a tumor suppressor in fallopian tube cancer, and potentially ovarian cancers, as a majority of them are derived from the fallopian tube epithelium. However, further studies are needed to understand the exact roles played by this kinase in these reproductive tissues. Citation Format: Mary A. Ndiaye, Shengqin Su, Rebecca M. Baus, Wei Huang, Manish S. Patankar, Nihal Ahmad. Potential tumor suppressor function of polo-like kinase 5 in ovarian cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1251.