The dark side of glucose transporters in prostate cancer: Are they a new feature to characterize carcinomas?

Abstract

One of the hallmarks of cancer cells is the increased ability to acquire nutrients, particularly glucose and glutamine. Proliferating cells need precursors for cell growth and NADPH reducing equivalents for survival. The principal responsible for glucose uptake is facilitative glucose transporters (GLUTs), which usually are overexpressed in cancer cells. Besides their role in glucose uptake, GLUT transporters are able to transport other compounds such as dehydroascorbic acid or uric acid. They play a major role in tumor progression and cellular processes such as regulated cell death. The prostate gland has the particular characteristic of being more glycolytic than other non-pathological tissues given an accumulation of citrate in the seminal fluid and the inhibition of m-aconitase that affects to tricarboxylic acid cycle. In prostate cancer (PCa), androgens increase glucose uptake, upregulate GLUT transporters such as GLUT1 and GLUT3 and stimulate AMP-activated protein kinase pathway, suggesting a possible connection between glycolytic and androgenic signaling. Interestingly, diabetes is not a risk factor for PCa, as it is in other cancers, while insulin stimulates progression and insulin-like growth factor 1 pathway plays an important role in PCa progression. It was recently found that PCa cells overexpress GLUT4 and, more importantly, that it seems to be related to the castration-resistant prostate cancer (CRPC) phenotype, although little is known about its participation in tumor progression. This review will focus on the role of GLUT transporters along with PCa progression, and the involvement of GLUT4 on CRPC phenotype transition would be considered.

GLUT1 protects prostate cancer cells from glucose deprivation-induced oxidative stress

“…In prostate cancer (PCa), glucose metabolism plays a major role in progression [14] . Androgens can activate the metabolic regulator AMP-activated kinase (AMPK), promoting oxidative phosphorylation (OXPHOS) [15] .…”

Vitamin C in combination with inhibition of mutant IDH1 synergistically activates TET enzymes and epigenetically modulates gene silencing in colon cancer cells

“…Frequently, cancer cells show a high expression of glucose transporters GLUT1 and GLUT3 due to the metabolic changes and high demands of energy through neoplastic transformation [43,55,56]. In IDH1 +/+ and IDH1 R132H/+ cells, GLUT1 and GLUT3 levels were reduced upon treatment with VC.…”

Regulation of Cellular Metabolism by High-Risk Human Papillomaviruses

“…Under hypoxia or nutrient deprivation, tumor cells overexpress at least one of the GLUT transporters, predominantly GLUT1. A high expression of this glucose transporter has been described in many types of cancer including cervical cancer [ 65 , 66 ]. It has been reported that GLUT1 is a transcriptional target of HIF1, which activates a panel of target genes for example GLUT-1, GLUT-3, carbonic anhydrase IX (CAIX), and vascular endothelial growth factor (VEGF), promoting the transcription of glycolytic enzymes [ 58 , 66 , 67 ].…”

“…A high expression of this glucose transporter has been described in many types of cancer including cervical cancer [ 65 , 66 ]. It has been reported that GLUT1 is a transcriptional target of HIF1, which activates a panel of target genes for example GLUT-1, GLUT-3, carbonic anhydrase IX (CAIX), and vascular endothelial growth factor (VEGF), promoting the transcription of glycolytic enzymes [ 58 , 66 , 67 ]. Cancer cells have a high demand of nutrients due to their high rate of proliferation, so the entry of glucose by facilitated diffusion through GLUT transporters could be insufficient, being required other mechanisms of glucose uptake may be required.…”

“…SGLT1 which is present in HPV-positive cervical carcinoma cells helps cells to accumulate glucose even when there is a low concentration of extracellular glucose [ 63 ]. In addition, in several tumors EGFR is highly expressed and this receptor is physically associated with SGLT1, inducing its stabilization and promoting glucose entry into cancer cells [ 64 , 65 , 66 , 69 ].…”