Glucose transporters in cancer metabolism

Abstract

Tumor cells exhibit elevated levels of glucose uptake, a phenomenon that has been capitalized upon for the prognostic and diagnostic imaging of a wide range of cancers using radio-labeled glucose analogs. We have, however, not yet been able to target glucose entry in a tumor cell-specific manner for therapy. GLUTs have been identified as rate-limiting in specific tumor contexts. The identification and targeting of tumor-specific GLUTs provide a promising approach to block glucose-regulated metabolism and signaling more comprehensively.

Glucose transporter 3 performs a critical role in mTOR-mediated oncogenic glycolysis and tumorigenesis

“…-/-MEFs expressing shGlut3 1 or shControl were injected into nude mice subcutaneously. Tsc2 -/-MEFs expressing shGlut3 1 exhibited substantially reduced tumorigenic and lethal capacity compared with the control cells (Fig.…”

“…To offset this disadvantage, the glycolytic rate in tumor cells is 100x higher than that in normal cells, and glucose uptake into tumor cells is also accelerated (1). A family of glucose transporters (Gluts) facilitates glucose movement across the plasma membranes in a tissue-specific manner, and 14 different Glut isoforms have been characterized at present (2).…”

Synthesis and Anticancer Activity of Glucosylated Podophyllotoxin Derivatives Linked via 4β-Triazole Rings

“…Due to their enhanced glucose consumption, cancer cells generally express higher levels of GLUTs than normal cells [22]. For example, glucose transporter class 1 (GLUT1) has been found to be overexpressed in a variety of both solid and hematological malignancies such as large B-cell lymphoma, colorectal carcinomas, hepatocellular carcinoma, head and neck cancer, gastrointestinal stromal tumor (GIST), prostate carcinoma, thyroid carcinoma, renal cell cancer, lung cancer, pancreatic cancer, sarcomas and laryngeal carcinomas [19]. Thus, in this study we planned to covalently link a glucose residue to podopyllotoxin so the resulting cytotoxic agents may be preferably taken up by cancer cells through the mediation of GLUTs.…”

“…Glucose is the main source of metabolic energy of animal cells, generating ATP through glycolysis and oxidative phosphorylation. Cancer cells are well known to display an enhanced uptake and consumption of glucose, which is metabolized primarily through the fermentative pathway instead of tricarboxylic acid cycle and oxidative phosphorylation in the mitochondria of normal cells [19]. The transport of glucose across the plasma membrane into the cytosol is mediated by a family of glucose transporters (GLUTs) [20,21].…”

Elmo2 Is a Regulator of Insulin-dependent Glut4 Membrane Translocation

“…Unlike other glucose transporters that constitutively reside on the plasma membrane, Glut4 is stored in intracellular compartments in the form of small membrane vesicles, termed Glut4 vesicles, at basal state and is only redistributed at the membrane upon insulin stimulation (13,14). As an insulinregulated glucose transporter, Glut4 plays a central role in the control of whole body glucose homeostasis and peripheral insulin sensitivity.…”