Abstract 3517: Role of primary cilia in breast and prostate cancer

Abstract

Abstract Primary cilia are microtubule-based organelles expressed on many mammalian cell types and help sense the extracellular environment. Signaling pathways important in development, tissue homeostasis, as well as cancer are known to be regulated by primary cilia, such as the Wnt and Hedgehog pathways. However, little is known about the role of primary cilia in cancer. We have previously demonstrated in a published study that primary cilia expression was significantly decreased through human prostate cancer progression (PLoS ONE 8 (7), 2013). We also discovered that primary cilia lengths were shorter through prostate cancer progression, which suggests dysfunction. In addition, we observed that primary cilia expression and length correlated with canonical Wnt signaling in normal human prostate tissue, premalignant lesions, and a subset of cancers. This data suggested that primary cilia dysfunction may alter Wnt signaling in the human prostate. We have also characterized primary cilia in human breast cancers, and similarly found a significant loss of primary cilia with breast cancer progression. We therefore hypothesize that primary cilia suppress tumorigenesis in these tissues, and consequently that primary cilia loss promotes cancer formation by altering signaling pathways. We are currently testing this hypothesis by knocking out primary cilia in a tumorigenic mammary mouse model and measuring changes in tumor growth, as well as changes in signaling pathways, like Wnt and Hedgehog signaling. Preliminary data demonstrates enhanced tumor growth in the absence of primary cilia, thus supporting our hypothesis that primary cilia may act as tumor suppressor organelles. Citation Format: Nadia B. Hassounah, Martha Nunez, Raymond Nagle, Kimberly M. McDermott. Role of primary cilia in breast and prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3517. doi:10.1158/1538-7445.AM2014-3517