Abstract 1180: Hexokinase II plays a pivotal role in colorectal cancer cell proliferation and survival

The Warburg Effect describes the widely observed metabolic phenotype of cancer cells and their heavy reliance on the glycolytic pathway for energy production regardless of oxygen tension. This is a result of alterations to metabolic signaling pathways leading to an upregulation in key glycolytic enzymes. Hexokinase II (HKII) catalyzes the first irreversible step of glycolysis and is often overexpressed in tumors. 3-bromopyruvate (3BP) has been shown to primarily target HKII, and is a promising anti-cancer compound capable of targeting critical metabolic pathways in cancer cells. Here we examine the importance of HKII to cell proliferation and survival and also whether its inhibition could provide a therapeutic strategy in human colorectal cancer (CRC). Initially, established human CRC cell lines (HCT116, Caco2, SW480, DLD-1) were screened for HKII mRNA and protein expression. Cell proliferation and survival following HKII inhibition via both siRNA and 3BP treatment was determined using crystal violet staining, flow cytometry and western blotting. Sensitivity to 3BP was correlated with HKII expression amongst the cell lines screened. We next examined the pro-survival AKT signaling pathway via western blotting and found that AKT phosphorylation was dependent on 3BP dose and was residue-specific. Immunofluorescence was then used to examine subcellular HKII localization. Following 3BP treatment, mitochondrial localization of HKII was lost. As a result of tumor vascular abnormalit...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Molecular and Cellular Biology Source Type: research