Abstract PR01: Role of mitochondrial folate transporter in metabolism of tumor cells

The objective of the present study is to identify modulators of cellular metabolism among transportome genes which could potentially be exploited as targets in pancreatic ductal adenocarcinoma (PDAC). Indeed cancer cells have the ability to adapt in order to survive stressful environment where oxygen and nutrients are limited due to the poor vasculature and outgrowth of stromal component. Thus, disrupting mechanisms of metabolic adaptation could inhibit tumor proliferation or sensitize tumor cells to treatment. Ion channels and transporters provide the link between cancer cells, stroma and matrix. Additionally these proteins may redirect metabolic fluxes among the cellular compartments which could provide alternative utilization of available substrates.We performed a Metabolic Flux Analyzer siRNA-based screen of transportome genes in Mia PaCa-2 cells to find transporters that influence either glycolysis (extracellular acidification rate) or oxidative phosphorylation (oxygen consumption rate). Among the hits SLC25A32 (Mitochondrial Folate Transporter) was identified to significantly increase oxygen consumption. SLC25A32 is poorly characterized in the literature and its function and role in tumorigenesis are currently unknown. The gene was shown to be expressed in the inner mitochondrial membrane and was identified as a bi-directional mitochondrial transporter of tetrahydroxyfolate (THF). Interestingly an inactivating mutation of SLC25A32 leads to glycine auxotrophy in CHO cell...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Therapeutic Targets From Cancer: Oral Presentations - Proffered Abstracts Source Type: research