Abstract 4434: Contribution of heterogenous ribonucleoprotein A18 in prostate cancer progression

Abstract

Abstract Prostate cancer is the third leading cause of cancer deaths among men in the United States, with recurrent metastasis being the predominant cause of mortality. In spite of the significant progress made in the past half century with hormonal therapy for metastatic prostate cancer, a majority eventually progresses to a lethal stage of the disease commonly known as castration-resistant prostate cancer. New treatment strategies are therefore needed. Previous work from our lab has identified the RNA-binding protein heterogenous ribonucleoprotein A18 (hnRNP A18) as a new regulator of protein translation in cancer cells. While its localization is predominantly nuclear, hnRNP A18 translocates out to the cytosol in response to cellular stress like hypoxia. Immunohistochemistry data from tissue microarrays reveals increased expression of hnRNP A18 in prostate hyperplasia, and even greater overexpression in prostate adenocarcinoma as compared to the surrounding normal tissue. Furthermore, a greater percentage of hnRNP A18 is seen to shift from the nucleus to the cytosol as the disease progresses. In the cytosol, hnRNP A18 recognizes and binds to a specific 51 nucleotide RNA motif in the 3' untranslated region of targeted transcripts, stabilizing them and enhancing their translation. Transcripts targeted by hnRNP A18 confer tumor growth advantages. The down-regulation of hnRNP A18 was seen to reduce cancer cell proliferation, migration, and invasion. Moreover, down-regulation of hnRNP A18 significantly reduces prostate cancer growth in a mouse tumor xenograft model. Taken together, our data suggests that hnRNP A18 could be a potentially new target to stop or limit prostate cancer progression. Citation Format: Elizabeth Tsuying Chang, Eun Yong Choi, Palak R. Parekh, France Carrier. Contribution of heterogenous ribonucleoprotein A18 in prostate cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4434.