Related Experiment Video
Updated: Jul 4, 2026

Analysis of SCAP N-glycosylation and Trafficking in Human Cells
Published on: November 8, 2016
The tuberous sclerosis complex regulates trafficking of glucose transporters and glucose uptake
Xiuyun Jiang1, Heidi Kenerson, Lauri Aicher
1Department of Surgery, Box 356410, University of Washington, 1959 NE Pacific, Seattle, WA 98195, USA.
Abstract:
Human cancers often display an avidity for glucose, a feature that is exploited in clinical staging and response monitoring by using (18)F-fluoro-deoxyglucose (FDG) positron emission tomography. Determinants of FDG accumulation include tumor blood flow, glucose transport, and glycolytic rate, but the underlying molecular mechanisms are incompletely understood. The phosphoinositide-3 kinase/Akt/mammalian target of rapamycin complex (mTORC) 1 pathway has been implicated in this process via the hypoxia-inducible factor alpha-dependent expression of vascular endothelial growth factor and glycolytic enzymes. Thus, we predicted that tumors with elevated mTORC1 activity would be accompanied by high FDG uptake. We tested this hypothesis in eight renal angiomyolipomas in which the loss of tuberous sclerosis complex (TSC) 1/2 function gave rise to constitutive mTORC1 activation. Surprisingly, these tumors displayed low FDG uptake on positron emission tomography. Exploring the underlying mechanisms in vitro revealed that Tsc2 regulates the membrane localization of the glucose transporter proteins (Glut)1, Glut2, and Glut4, and, therefore, glucose uptake. Down-regulation of cytoplasmic linker protein 170, an mTOR effector, rescued Glut4 trafficking in Tsc2(-/-) cells, whereas up-regulation of Akt activity in these cells was insufficient to redistribute Glut4 to the plasma membrane. The effect of mTORC1 on glucose uptake was confirmed using a liver-specific Tsc1- deletion mouse model in which FDG uptake was reduced in the livers of mutant mice compared with wild-type controls. Together, these data show that mTORC1 activity is insufficient for increased glycolysis in tumors and that constitutive mTOR activity negatively regulates glucose transporter trafficking.
Related Concept Videos
Glucose Transporters
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Glucose Absorption Into the Small Intestine
Secondary Active Transport
Secondary Active Transport
Membrane Proteins
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
