Abstract 5387: Integrative analysis of transcriptomic and metabolomic data reveals a critical role for aminosugar metabolism in prostate cancer.

Abstract

Abstract Prostate Cancer is the second most common cause of cancer-related death in men in the US. Like other tumors, prostate cancer development and progression is dictated by multiple molecular events that include changes in levels of genes, transcripts, proteins and metabolites. To better understand the biology of prostate cancer development it is essential to integrate these disparate yet related datasets. Our laboratory has identified matched transcriptomic, proteomic and metabolomic changes in localized prostate cancer relative to adjacent benign tissue as well in metastatic disease compared to organ-confined tumor. To study this using a System's Biology approach we have recently embarked on a pilot study aimed at integrating transcriptomic and metabolomic data to obtain biochemical pathways that key to prostate cancer development. Using an in-house network-based enrichment strategy, amino sugar metabolism was found to be significantly enriched in organ-confined prostate cancer but not in metastatic disease. Amino sugar metabolism describes the utilization of glucose-derived carbon and amino acid (mostly glutamine)-derive nitrogen to produce glucosamines. These amino sugars participate in synthesis of immune modulatory compounds as well as in glycosylation cascades. In this study, we describe the molecular analyses of Glucosamine-6 phosphate-N-acetyl Transferase (GNPNAT1), a key enzyme that converts D-glucosamine 6-phosphate to N-acetyl-D-glucosamine 6-phosphate, in prostate cancer. Our results indicate upregulation of GNPNAT1 in organ-confined prostate cancer as compared to benign adjacent tissue as well as metastatic tissue and regulation of the pathway by androgen. Stable knockdown of GNPNAT1 in androgen dependent LNCap cells leads to diminished cell growth and cell cycle arrest. In contrast, growth and cell cycle are not affected by the knockdown of GNPNAT1 in androgen independent C4-2 cells. Knockdown of GNPNAT1 in C4-2 cells enhances invasiveness which is not observed in LNCap knockdown cells. In this work we show that GNPNAT1 is linked to androgen receptor (AR) action and thus is a critical enzyme for the survival of androgen dependent prostate cancer cells. Citation Format: Katrin Panzitt, Ali Shojaie, Nagireddy Putluri, Sumanta Basu, Vasanta Putluri, Susmita Samanta, Michael Ittmann, Ismael Vergara, George Michailidis, Ganesh Palapattu, Arun Sreekumar. Integrative analysis of transcriptomic and metabolomic data reveals a critical role for aminosugar metabolism in prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5387. doi:10.1158/1538-7445.AM2013-5387