Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer

Abstract

Malignant cells are known to have accelerated metabolism, high glucose requirements, and increased glucose uptake. Transport of glucose across the plasma membrane of mammalian cells is the first rate-limiting step for glucose metabolism and is mediated by facilitative glucose transporter (GLUT) proteins. Increased glucose transport in malignant cells has been associated with increased and deregulated expression of glucose transporter proteins, with overexpression of GLUT1 and/or GLUT3 a characteristic feature. Oncogenic transformation of cultured mammalian cells causes a rapid increase of glucose transport and GLUT1 expression via interaction with GLUT1 promoter enhancer elements. In human studies, high levels of GLUT1 expression in tumors have been associated with poor survival. Studies indicate that glucose transport in breast cancer is not fully explained by GLUT1 or GLUT3 expression, suggesting involvement of another glucose transporter. Recently, a novel glucose transporter protein, GLUT12, has been found in breast and prostate cancers. In human breast and prostate tumors and cultured cells, GLUT12 is located intracellularly and at the cell surface. Trafficking of GLUT12 to the plasma membrane could therefore contribute to glucose uptake. Several factors have been implicated in the regulation of glucose transporter expression in breast cancer. Hypoxia can increase GLUT1 levels and glucose uptake. Estradiol and epidermal growth factor, both of which can play a role in breast cancer cell growth, increase glucose consumption. Estradiol and epidermal growth factor also increase GLUT12 protein levels in cultured breast cancer cells. Targeting GLUT12 could provide novel methods for detection and treatment of breast and prostate cancer.

Glycogen synthase kinase-3β positively regulates the proliferation of human ovarian cancer cells

“…It is well known that malignant cells have accelerated metabolism and high glucose requirements [25], and that tumors consistently rely on anaerobic pathways to convert glucose to ATP even in the presence of abundant oxygen [26], and that tumor cells maintain ATP production by increasing glucose influx to fuel the energy requirements of unrestricted proliferation [25]. Thus, activated GSK-3β in ovarian cancer may contribute to high consumption of glucose through inhibition of glycogen synthesis, thereby promoting ovarian cancer cell proliferation.…”

Expression analysis of facilitative glucose transporters (GLUTs) in human thyroid carcinoma cell lines and primary tumors

“…Genes encoding for these transporters belong to the solute carrier 2A family and are classified in three groups: class I (GLUT1-GLUT4), class II which includes the fructose transporter GLUT5 and isoforms GLUT7, M a n u s c r i p t 4 GLUT9, GLUT11. Class III (GLUT6, GLUT8, GLUT10, GLUT12 and the H + /myoinositol transporter HMIT) (Joost et al, 2002, Joost and Thorens, 2001, Macheda et al, 2005. Since the enhanced ability in glucose uptake of tumor cells correlates with an increased expression of GLUTs, these transporters have been characterized in various tumor cell lines and in particular in lines derived from breast cancer (Macheda et al, 2005).…”

“…Class III (GLUT6, GLUT8, GLUT10, GLUT12 and the H + /myoinositol transporter HMIT) (Joost et al, 2002, Joost and Thorens, 2001, Macheda et al, 2005. Since the enhanced ability in glucose uptake of tumor cells correlates with an increased expression of GLUTs, these transporters have been characterized in various tumor cell lines and in particular in lines derived from breast cancer (Macheda et al, 2005). Up to date, only two tumoral thyroid cell lines TPC-1 (papillary thyroid carcinoma) and FTC-133 (follicular thyroid carcinoma), have been analyzed for the expression of few GLUT isoforms (Matsuzu et al, 2005).…”

Proliferating cell nuclear antigen in the cytoplasm interacts with components of glycolysis and cancer

“…Cancer cells generally show an increase in glucose metabolism, compared to normal cells [19][20][21][22]. This may be, in part, due to the increase in the glucose trans-membrane transportation and concentration of glycolytic enzymes in cancer cells [23][24][25].…”