Glucose-dependent glucose transporter 1 expression and its impact on viability of thyroid cancer cells

Jóźwiak,Paweł; Krześlak,Anna; Bryś,Magdalena; Lipińska,Anna

doi:10.3892/or.2014.3673

Glucose-dependent glucose transporter 1 expression and its impact on viability of thyroid cancer cells

Authors:
- Paweł Jóźwiak
- Anna Krześlak
- Magdalena Bryś
- Anna Lipińska
View Affiliations

Affiliations: Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland
Published online on: December 12, 2014 https://doi.org/10.3892/or.2014.3673
Pages: 913-920

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Cancer cells exhibit an altered metabolism characterized by enhanced glycolysis and glucose consumption. In glucose‑addicted cancer cells upregulation of glucose transport across the plasma membrane is mediated by a family of facilitated glucose transporter proteins, particularly glucose transporter 1 (GLUT1). The aim of the present study was to investigate the impact of GLUT1 expression on glucose uptake and viability of FTC-133 and 8305c thyroid cancer cells growing in hypoglycemic, normoglycemic and hyperglycemic conditions. The results showed that the total expression of GLUT1 was higher in the two cell types growing in low glucose compared to cells growing in normoglycemia or hyperglycemia and this was correlated with AKT Ser473 phosphorylation but not with the expression of hypoxia inducible factor α (HIF1α). However, the membrane expression of GLUT1 was correlated with HIF1α expression. HIF1α expression was positively correlated with the glucose concentration in FTC-133 cells, whereas this expression was inversely correlated in 8305c cells. Glucose uptake was dependent on the membrane level of GLUT1 but not total GLUT1 expression. Downregulation of GLUT1 expression by RNAi in FTC-133 cells caused a reduction in glucose uptake but did not significantly affect cell viability. In the case of 8305c cells showing low endogenous GLUT1 expression and lack of HIF1α expression in normoxic conditions GLUT1 RNAi impacted cell viability. These data suggested that GLUT1 may be part of an AKT1-dependent mechanism allowing cells to survive in low levels of glucose. Glucose concentration inversely affected HIF1α expression and the level of GLUT1 in membrane as well as glucose uptake in FTC-133 and 8305c cells. The extent of GLUT1 impact on cell viability was also cell-type-dependent.

View Figures

View References

1	Dang CV: Links between metabolism and cancer. Genes Dev. 26:877–890. 2012. View Article : Google Scholar : PubMed/NCBI
2	Bensinger SJ and Christofk HR: New aspects of the Warburg effect in cancer cell biology. Semin Cell Dev Biol. 23:352–361. 2012. View Article : Google Scholar : PubMed/NCBI
3	Graham NA, Tahmasian M, Kohli B, Komisopoulou E, Zhu M, Vivanco I, Teitell MA, Wu H, Ribas A, Lo RS, Mellinghoff IK, Mischel PS and Graeber TG: Glucose deprivation activates a metabolic and signaling amplification loop leading to cell death. Mol Syst Biol. 8:5892012. View Article : Google Scholar : PubMed/NCBI
4	Palorini R, Cammarata FP, Balestrieri C, Monestiroli A, Vasso M, Gelfi C, Alberghina L and Chiaradonna F: Glucose starvation induces cell death in K-ras-transformed cells by interfering with the hexosamine biosynthesis pathway and activating the unfolded protein response. Cell Death Dis. 4:e7322013. View Article : Google Scholar : PubMed/NCBI
5	Mendivil-Perez M, Jimenez-Del-Rio M and Velez-Pardo C: Glucose starvation induces apoptosis in a model of acute T leukemia dependent on caspase-3 and apoptosis-inducing factor: a therapeutic strategy. Nutr Cancer. 65:99–109. 2013. View Article : Google Scholar : PubMed/NCBI
6	Ganapathy V, Thangaraju M and Prasad PD: Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. Pharmacol Ther. 121:29–40. 2009. View Article : Google Scholar
7	Adekola K, Rosen ST and Shanmugam M: Glucose transporters in cancer metabolism. Curr Opin Oncol. 24:650–654. 2012. View Article : Google Scholar : PubMed/NCBI
8	Jóźwiak P and Lipińska A: The role of glucose transporter 1 (GLUT1) in the diagnosis and therapy of tumors. Postepy Hig Med Dosw. 66:165–174. 2012.(In Polish).
9	Szablewski L: Expression of glucose transporters in cancers. Biochim Biophys Acta. 1835:164–169. 2013.
10	Calvo MB, Figueroa A, Pulido EG, Campelo RG and Aparicio LA: Potential role of sugar transporters in cancer and their relationship with anticancer therapy. Int J Endocrinol. 2010:pii: 205357. 2010.PubMed/NCBI
11	Mori Y, Tsukinoki K, Yasuda M, Miyazawa M, Kaneko A and Watanabe Y: Glucose transporter type 1 expression are associated with poor prognosis in patients with salivary gland tumors. Oral Oncol. 43:563–569. 2007. View Article : Google Scholar
12	Chung FY, Huang MY, Yeh CS, Chang HJ, Cheng TL, Yen LC, Wang JY and Lin SR: GLUT1 gene is a potential hypoxic marker in colorectal cancer patients. BMC Cancer. 9:2412009. View Article : Google Scholar : PubMed/NCBI
13	Krzeslak A, Wojcik-Krowiranda K, Forma E, Jozwiak P, Romanowicz H, Bienkiewicz A and Brys M: Expression of GLUT1 and GLUT3 glucose transporters in endometrial and breast cancers. Pathol Oncol Res. 18:721–728. 2012. View Article : Google Scholar : PubMed/NCBI
14	Sasaki H, Shitara M, Yokota K, Hikosaka Y, Moriyama S, Yano M and Fujii Y: Overexpression of GLUT1 correlates with Kras mutations in lung carcinomas. Mol Med Rep. 5:599–602. 2012.
15	Cho H, Lee YS, Kim J, Chung JY and Kim JH: Overexpression of glucose transporter-1 (GLUT-1) predicts poor prognosis in epithelial ovarian cancer. Cancer Invest. 31:607–615. 2013. View Article : Google Scholar : PubMed/NCBI
16	Jóźwiak P, Krześlak A, Pomorski L and Lipińska A: Expression of hypoxia-related glucose transporters GLUT1 and GLUT3 in benign, malignant and non-neoplastic thyroid lesions. Mol Med Rep. 6:601–606. 2012.
17	Monti E and Gariboldi MB: HIF-1 as a target for cancer chemotherapy, chemosensitization and chemoprevention. Curr Mol Pharmacol. 14:62–77. 2011. View Article : Google Scholar
18	Mills KT, Bellows CF, Hoffman AE, Kelly TN and Gagliardi G: Diabetes mellitus and colorectal cancer prognosis: a meta-analysis. Colon Rectum Dis. 56:1304–1319. 2013. View Article : Google Scholar
19	Zhu Z, Wang X, Shen Z, Lu Y, Zhong S and Xu C: Risk of bladder cancer in patients with diabetes mellitus: an updated meta-analysis of 36 observational studies. BMC Cancer. 13:3102013. View Article : Google Scholar : PubMed/NCBI
20	Yun J, Rago C, Cheong I, Pagliarini R, Angenendt P, Rajagopalan H, Schmidt K, Willson JK, Markowitz S, Zhou S, Diaz LA, Velculescu VE, Lengauer C, Kinzler KW, Vogelstein B and Papadopoulos N: Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science. 325:1555–1559. 2009. View Article : Google Scholar : PubMed/NCBI
21	Andersen DK: Diabetes and cancer: placing the association in perspective. Curr Opin Endocrinol Diabetes Obes. 20:81–86. 2013. View Article : Google Scholar : PubMed/NCBI
22	Shikata K, Ninomiya T and Kiyohara Y: Diabetes mellitus and cancer risk: review of the epidemiological evidence. Cancer Sci. 104:9–14. 2013. View Article : Google Scholar
23	De Pergola G and Silvestris F: Obesity as a major risk factor for cancer. J Obes. 2013:2915462013. View Article : Google Scholar : PubMed/NCBI
24	Li W, Ma Q, Liu J, Han L, Ma G, Liu H, Shan T, Xie K and Wu E: Hyperglycemia as a mechanism of pancreatic cancer metastasis. Front Biosci. 17:1761–1774. 2012. View Article : Google Scholar
25	Shih SR, Chiu WY, Chang TC and Tseng CH: Diabetes and thyroid cancer risk: literature review. Exp Diabetes Res. 2012:5782852012. View Article : Google Scholar : PubMed/NCBI
26	Yamada K, Saito M, Matsuoka H and Inagaki N: A real-time method of imaging glucose uptake in single, living mammalian cells. Nat Protoc. 2:753–762. 2007. View Article : Google Scholar : PubMed/NCBI
27	Ren BF, Deng LF, Wang J, Zhu YP, Wei L and Zhou Q: Hypoxia regulation of facilitated glucose transporter-1 and glucose transporter-3 in mouse chondrocytes mediated by HIF-1α. Joint Bone Spine. 75:176–181. 2008. View Article : Google Scholar
28	Lidgren A, Bergh A, Grankvist K, Rasmuson T and Ljungberg B: Glucose transporter-1 expression in renal cell carcinoma and its correlation with hypoxia inducible factor-1α. BJU Int. 101:480–484. 2008.
29	Baumann MU, Zamudio S and Illsley NP: Hypoxic upregulation of glucose transporters in BeWo choriocarcinoma cells is mediated by hypoxia-inducible factor-1. Am J Physiol Cell Physiol. 293:C477–C485. 2007. View Article : Google Scholar : PubMed/NCBI
30	Iida T, Yasuda M, Miyazawa M, Fujita M, Osamura RY, Hirasawa T, Muramatsu T, Murakami M, Saito K and Mikami M: Hypoxic status in ovarian serous and mucinous tumors: relationship between histological characteristics and HIF-1α/GLUT-1 expression. Arch Gynecol Obstet. 277:539–546. 2008. View Article : Google Scholar
31	Yasuda M, Miyazawa M, Fujita M, Kajiwara H, Iida T, Hirasawa T, Muramatsu T, Murakami M, Mikami M, Saitoh K, Shimizu M, Takekoshi S and Osamura RY: Expression of hypoxia inducible factor-1α (HIF-1α) and glucose transporter-1 (GLUT-1) in ovarian adenocarcinomas: Difference in hypoxic status depending on histological character. Oncol Rep. 19:111–116. 2008.
32	Liu Y, Li YM, Tian RF, Liu WP, Fei Z, Long QF, Wang XA and Zhang X: The expression and significance of HIF-1α and GLUT-3 in glioma. Brain Res. 1304:149–154. 2009. View Article : Google Scholar : PubMed/NCBI
33	Wu XH, Chen SP, Mao JY, Ji XX, Yao HT and Zhou SH: Expression and significance of hypoxia-inducible factor-1α and glucose transporter-1 in laryngeal carcinoma. Oncol Lett. 5:261–266. 2013.
34	Bos R, van Der Hoeven JJ, van Der Wall E, van Der Groep P, van Diest PJ, Comans EF, Joshi U, Semenza GL, Hoekstra OS, Lammertsma AA and Molthoff CF: Biologic correlates of ¹⁸fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J Clin Oncol. 20:379–387. 2002. View Article : Google Scholar : PubMed/NCBI
35	Flier JS, Mueckler MM, Usher P and Lodish HF: Elevated levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes. Science. 235:1492–1495. 1987. View Article : Google Scholar : PubMed/NCBI
36	Osthus RC, Shim H, Kim S, Li Q, Reddy R, Mukherjee M, Xu Y, Wonsey D, Lee LA and Dang CV: Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc. J Biol Chem. 275:21797–21800. 2000. View Article : Google Scholar : PubMed/NCBI
37	Zhang C, Liu J, Liang Y, Wu R, Zhao Y, Hong X, Lin M, Yu H, Liu L, Levine AJ, Hu W and Feng Z: Tumour-associated mutant p53 drives the Warburg effect. Nat Commun. 4:29352013.PubMed/NCBI
38	Elstrom RL, Bauer DE, Buzzai M, Karnauskas R, Harris MH, Plas DR, Zhuang H, Cinalli RM, Alavi A, Rudin CM and Thompson CB: Akt stimulates aerobic glycolysis in cancer cells. Cancer Res. 64:3892–3899. 2004. View Article : Google Scholar : PubMed/NCBI
39	Viglietto G, Amodio N, Malanga D, Scrima M and De Marco C: Contribution of PKB/AKT signaling to thyroid cancer. Front Biosci. 16:1461–1487. 2011. View Article : Google Scholar
40	Cassinelli G, Zuco V, Gatti L, Lanzi C, Zaffaroni N, Colombo D and Perego P: Targeting the Akt kinase to modulate survival, invasiveness and drug resistance of cancer cells. Curr Med Chem. 20:1923–1945. 2013. View Article : Google Scholar : PubMed/NCBI
41	Gao M, Liang J, Lu Y, Guo H, German P, Bai S, Jonasch E, Yang X, Mills GB and Ding Z: Site-specific activation of AKT protects cells from death induced by glucose deprivation. Oncogene. 33:745–755. 2014. View Article : Google Scholar
42	Priebe A, Tan L, Wahl H, Kueck A, He G, Kwok R, Opipari A and Liu JR: Glucose deprivation activates AMPK and induces cell death through modulation of Akt in ovarian cancer cells. Gynecol Oncol. 122:389–395. 2011. View Article : Google Scholar : PubMed/NCBI
43	Mathews EH, Stander BA, Joubert AM and Liebenberg L: Tumor cell culture survival following glucose and glutamine deprivation at typical physiological concentrations. Nutrition. 30:218–227. 2014. View Article : Google Scholar
44	Young CD, Lewis AS, Rudolph MC, Ruehle MD, Jackman MR, Yun UJ, Ilkun O, Pereira R, Abel ED and Anderson SM: Modulation of glucose transporter 1 (GLUT1) expression levels alters mouse mammary tumor cell growth in vitro and in vivo. PLoS One. 6:e232052011. View Article : Google Scholar : PubMed/NCBI
45	Li S, Yang X, Wang P and Ran X: The effects of GLUT1 on the survival of head and neck squamous cell carcinoma. Cell Physiol Biochem. 32:624–634. 2013. View Article : Google Scholar : PubMed/NCBI