Glucose transporter 1 (GLUT1) is a facilitative glucose transporter overexpressed in various types of tumors; thus, it has been considered as an important target for cancer therapy.
HCC, such as other cancer types, presents a clinically well-known upregulation of several glycolytic key enzymes and proteins, including glucose transporters particularly glucose transporter 1 (GLUT1).
Remarkably, in the cancer group, memory T cells stimulated via CD3/CD28 under hypoxia failed to increase CD71 and Glut1 expression levels compared to the cells receiving anti-CD3 stimulation, a phenomenon that contrasted with the behaviour of memory T cells from nonmalignant effusions.
In pancreatic cancer, the loss of SIRT1 is accompanied by a decreased expression of proteins in the glycolysis pathway, such as GLUT1, and cancer cell proliferation.
Then, we review the current state-of-the-art of resveratrol and other natural products as GLUT1 inhibitors, focusing on those directed at treating different types of cancer.
Being a fundamental player in cancer metabolism, glucose transporter 1 (GLUT1) could be utilized as a prognostic biomarker that could fuel development of new treatment strategies.
The Cancer Genome Atlas analysis confirmed that patients with a favorable immune and metabolic gene signature (high CD8A, high COX5B, low GLUT1) had improved short- and long-term survival.
Whether the aberrant expression of microRNAs contributes to cancer metabolism is not fully understood. miR-328 is a putative potential target of SLC2A1, but the regulating mechanism between them remains unknown.
This interest is related to the importance of the GLUTs as archetypical membrane transport facilitators, as key limiters of the supply of glucose to cell metabolism, as targets of cell insulin and exercise signalling and of regulated membrane traffic, and as potential drug targets to combat cancer and metabolic diseases such as type 2 diabetes and obesity.
In this updated review, we examine the current scenario of the GLUTs as strategic targets in cancer and the unique concepts for discovery and development of GLUTs-targeted anticancer agents.
The leading compound <b>6d</b>, the IC<sub>50</sub> of which with the GLUT1 inhibitor 4,6-oethylidene-α-D-glucose (EDG) and phloretin (31.80 and 38.71 μM) are 36- and 44-folds higher, respectively, than the 48 h IC<sub>50</sub> (0.89 μM), is superior to the reported <b>5</b>-<b>8</b>, exhibiting enhanced cancer targeting.
The staining score of hypoxia marker Glut-1 in cancer cells was significantly higher in cases with CAIX (+) CAFs than in those with CAIX (-) CAFs (median: 20 vs. 0, p<0.01).