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Glut1 promotes cell proliferation, migration and invasion by regulating epidermal growth factor receptor and integrin signaling in triple-negative breast cancer cells

  • Oh, Sunhwa (Department of Life Science, Hanyang University) ;
  • Kim, Hyungjoo (Department of Life Science, Hanyang University) ;
  • Nam, KeeSoo (Department of Life Science, Hanyang University) ;
  • Shin, Incheol (Department of Life Science, Hanyang University)
  • Received : 2016.11.11
  • Accepted : 2016.12.06
  • Published : 2017.03.31

Abstract

Elevated glucose levels in cancer cells can be attributed to increased levels of glucose transporter (GLUT) proteins. Glut1 expression is increased in human malignant cells. To investigate alternative roles of Glut1 in breast cancer, we silenced Glut1 in triple-negative breast-cancer cell lines using a short hairpin RNA (shRNA) system. Glut1 silencing was verified by Western blotting and qRT-PCR. Knockdown of Glut1 resulted in decreased cell proliferation, glucose uptake, migration, and invasion through modulation of the EGFR/MAPK signaling pathway and integrin ${\beta}1$/Src/FAK signaling pathways. These results suggest that Glut1 not only plays a role as a glucose transporter, but also acts as a regulator of signaling cascades in the tumorigenesis of breast cancer.

Keywords

References

  1. Warburg O (1956) On the origin of cancer cells. Science 123, 309-314 https://doi.org/10.1126/science.123.3191.309
  2. Cairns RA, Harris IS and Mak TW (2011) Regulation of cancer cell metabolism. Nat Rev Cancer 11, 85-95 https://doi.org/10.1038/nrc2981
  3. Wood IS and Trayhurn P (2003) Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr 89, 3-9
  4. Kunkel M, Reichert TE, Benz P et al (2003) Overexpression of Glut-1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral squamous cell carcinoma. Cancer 97, 1015-1024 https://doi.org/10.1002/cncr.11159
  5. Kang SS, Chun YK, Hur MH et al (2002) Clinical significance of glucose transporter 1 (GLUT1) expression in human breast carcinoma. Jpn J Cancer Res 93, 1123-1128 https://doi.org/10.1111/j.1349-7006.2002.tb01214.x
  6. Brenton JD, Carey LA, Ahmed AA and Caldas C (2005) Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol 23, 7350-7360 https://doi.org/10.1200/JCO.2005.03.3845
  7. Perou CM, Sorlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406, 747-752 https://doi.org/10.1038/35021093
  8. Badve S, Dabbs DJ, Schnitt SJ et al (2011) Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists. Mod Pathol 24, 157-167 https://doi.org/10.1038/modpathol.2010.200
  9. Hussein YR, Bandyopadhyay S, Semaan A et al (2011) Glut-1 Expression Correlates with Basal-like Breast Cancer. Transl Oncol 4, 321-327 https://doi.org/10.1593/tlo.11256
  10. Nielsen TO, Hsu FD, Jensen K et al (2004) Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10, 5367-5374 https://doi.org/10.1158/1078-0432.CCR-04-0220
  11. Olayioye MA, Neve RM, Lane HA and Hynes NE (2000) The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 19, 3159-3167 https://doi.org/10.1093/emboj/19.13.3159
  12. Dhillon AS, Hagan S, Rath O and Kolch W (2007) MAP kinase signalling pathways in cancer. Oncogene 26, 3279-3290 https://doi.org/10.1038/sj.onc.1210421
  13. Lee CH, Yun HJ, Kang HS and Kim HD (1999) ERK/MAPK pathway is required for changes of cyclin D1 and B1 during phorbol 12-myristate 13-acetate-induced differentiation of K562 cells. IUBMB Life 48, 585-591 https://doi.org/10.1080/713803574
  14. Baldin V, Lukas J, Marcote MJ, Pagano M and Draetta G (1993) Cyclin D1 is a nuclear protein required for cell cycle progression in G1. Genes Dev 7, 812-821 https://doi.org/10.1101/gad.7.5.812
  15. Altenberg B and Greulich KO (2004) Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes. Genomics 84, 1014-1020 https://doi.org/10.1016/j.ygeno.2004.08.010
  16. Yang W, Zheng Y, Xia Y et al (2012) ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect. Nat Cell Biol 14, 1295-1304 https://doi.org/10.1038/ncb2629
  17. Shackelford DB and Shaw RJ (2009) The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer 9, 563-575 https://doi.org/10.1038/nrc2676
  18. Juliano RL and Haskill S (1993) Signal transduction from the extracellular matrix. J Cell Biol 120, 577-585 https://doi.org/10.1083/jcb.120.3.577
  19. Clark EA and Brugge JS (1995) Integrins and signal transduction pathways: the road taken. Science 268, 233-239 https://doi.org/10.1126/science.7716514
  20. Guan JL (1997) Role of focal adhesion kinase in integrin signaling. Int J Biochem Cell Biol 29, 1085-1096 https://doi.org/10.1016/S1357-2725(97)00051-4
  21. Mitra SK and Schlaepfer DD (2006) Integrin-regulated FAK-Src signaling in normal and cancer cells. Curr Opin Cell Biol 18, 516-523 https://doi.org/10.1016/j.ceb.2006.08.011
  22. Nagano O and Saya H (2004) Mechanism and biological significance of CD44 cleavage. Cancer Sci 95, 930-935 https://doi.org/10.1111/j.1349-7006.2004.tb03179.x
  23. Grover-McKay M, Walsh SA, Seftor EA, Thomas PA and Hendrix MJ (1998) Role for glucose transporter 1 protein in human breast cancer. Pathol Oncol Res 4, 115-120 https://doi.org/10.1007/BF02904704
  24. Schlaepfer DD, Mitra SK and Ilic D (2004) Control of motile and invasive cell phenotypes by focal adhesion kinase. Biochim Biophys Acta 1692, 77-102 https://doi.org/10.1016/j.bbamcr.2004.04.008
  25. Klingbeil P, Natrajan R, Everitt G et al (2010) CD44 is overexpressed in basal-like breast cancers but is not a driver of 11p13 amplification. Breast Cancer Res Treat 120, 95-109 https://doi.org/10.1007/s10549-009-0380-7
  26. Xu H, Tian Y, Yuan X et al (2016) Enrichment of CD44 in basal-type breast cancer correlates with EMT, cancer stem cell gene profile, and prognosis. Onco Targets Ther 9, 431-444
  27. Jordan M and Wurm F (2004) Transfection of adherent and suspended cells by calcium phosphate. Methods 33, 136-143 https://doi.org/10.1016/j.ymeth.2003.11.011

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