Membrane transporters in cell physiology, cancer metabolism and drug response

Abstract

By controlling the passage of small molecules across lipid bilayers, membrane transporters influence not only the uptake and efflux of nutrients, but also the metabolic state of the cell. With more than 450 members, the Solute Carriers (SLCs) are the largest transporter super-family, clustering into families with different substrate specificities and regulatory properties. Cells of different types are, therefore, able to tailor their transporter expression signatures depending on their metabolic requirements, and the physiological importance of these proteins is illustrated by their mis-regulation in a number of disease states. In cancer, transporter expression is heterogeneous, and the SLC family has been shown to facilitate the accumulation of biomass, influence redox homeostasis, and also mediate metabolic crosstalk with other cell types within the tumour microenvironment. This Review explores the roles of membrane transporters in physiological and malignant settings, and how these roles can affect drug response, through either indirect modulation of sensitivity or the direct transport of small-molecule therapeutic compounds into cells.

Predicting substrates for orphan Solute Carrier Proteins using multi-omics datasets

“…Solute carriers are known to play an important role in determining drug pharmacokinetics, safety and efficacy profiles (Alam et al, 2023). A key goal of the recently established International Transporter Consortium is to identify key transporters involved in drug transport and highlight potential issues around adverse drug-drug interactions involving transporters during clinical trials.…”

An Untargeted Metabolomics Strategy to Identify Substrates of Known and Orphan E. coli Transporters

“…Transport systems, which selectively move substrates across cell membranes, constitute an important component of bacterial physiology. The ability to manipulate bacterial transporters both genetically and chemically has applications in both medicine (as a major component of antibiotic resistance due to evolved adaptations in efflux transporters [ 1 , 2 , 3 , 4 ]) and microbial cell factories (as a reliable way to increase product yield and tolerance of toxic products to increase efflux from the intracellular space into the extracellular medium [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]). Transporters are similarly required to maximize substrate uptake [ 13 , 14 , 15 , 16 ].…”