The Interaction of GLUT1 and FOXM1 Leads to a Poor Prognosis in Colorectal Cancer

Author(s): Xiao-Yi Kuai, Zhi-Yi Lei*, Xiao-Shuang Liu, Xin-Yu Shao*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 20 , Issue 8 , 2020


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: Colorectal Cancer (CRC) is one of the most common fatal diseases with high morbidity. Alteration of glucose metabolism is one of the hallmarks in the development of CRC. Glucose Transporter 1 (GLUT1) is a key rate-limiting protein in hyperactive glucose metabolism and up-regulated in CRC, however, the underlying mechanism of the altered metabolism in CRC is still unknown.

Methods: In this study, immunohistochemical staining was used to evaluate the expression of GLUT1 and FOXM1 in 135 paired CRC and adjacent normal tissues. The association between the expression of GLUT1/FOXM1 and clinicopathological factors was determined and the correlation between GLUT1 and FOXM1 in CRC was investigated.

Results: Our results revealed that regardless of tumor location, GLUT1 and FOXM1 were overexpressed in CRC tissues, especially in patients with positive lymph node metastasis and TNM stage III-IV. Furthermore, GLUT1 showed a significantly strong link with FOXM1 in CRC tissue.

Conclusion: Overexpression of GLUT1 and FOXM1 may play critical roles in CRC leading to a poor prognosis.

Keywords: Colorectal cancer, FOXM1, GLUT1, prognosis, altered metabolism, immunohistochemical staining.

[1]
Brody, H. Colorectal cancer. Nature, 2015, 521(7551), S1.
[http://dx.doi.org/10.1038/521S1a] [PMID: 25970450]
[2]
Siegel, R.; Desantis, C.; Jemal, A. Colorectal cancer statistics, 2014. CA Cancer J. Clin., 2014, 64(2), 104-117.
[http://dx.doi.org/10.3322/caac.21220] [PMID: 24639052]
[3]
Okugawa, Y.; Grady, W.M.; Goel, A. Epigenetic alterations in colorectal cancer: Emerging biomarkers. Gastroenterology, 2015, 149(5), 1204-1225.e12.
[http://dx.doi.org/10.1053/j.gastro.2015.07.011] [PMID: 26216839]
[4]
Liberti, M.V.; Locasale, J.W. The warburg effect: How does it benefit cancer cells? Trends Biochem. Sci., 2016, 41(3), 211-218.
[http://dx.doi.org/10.1016/j.tibs.2015.12.001] [PMID: 26778478]
[5]
Zhang, M.; Liu, T.; Sun, H.; Weng, W.; Zhang, Q.; Liu, C.; Han, Y.; Sheng, W. Pim1 supports human colorectal cancer growth during glucose deprivation by enhancing the Warburg effect. Cancer Sci., 2018, 109(5), 1468-1479.
[http://dx.doi.org/10.1111/cas.13562] [PMID: 29516572]
[6]
Warburg, O.; Wind, F.; Negelein, E. The metabolism of tumors in the body. J. Gen. Physiol., 1927, 8(6), 519-530.
[http://dx.doi.org/10.1085/jgp.8.6.519] [PMID: 19872213]
[7]
Danhier, P.; Bański, P.; Payen, V.L.; Grasso, D.; Ippolito, L.; Sonveaux, P.; Porporato, P.E. Cancer metabolism in space and time: Beyond the Warburg effect. Biochim. Biophys. Acta Bioenerg., 2017, 1858(8), 556-572.
[http://dx.doi.org/10.1016/j.bbabio.2017.02.001] [PMID: 28167100]
[8]
Deng, D.; Xu, C.; Sun, P.; Wu, J.; Yan, C.; Hu, M.; Yan, N. Crystal structure of the human glucose transporter GLUT1. Nature, 2014, 510(7503), 121-125.
[http://dx.doi.org/10.1038/nature13306] [PMID: 24847886]
[9]
Shen, Y.M.; Arbman, G.; Olsson, B.; Sun, X.F. Overexpression of GLUT1 in colorectal cancer is independently associated with poor prognosis. Int. J. Biol. Markers, 2011, 26(3), 166-172.
[http://dx.doi.org/10.5301/JBM.2011.8550] [PMID: 21786248]
[10]
Wang, J.; Ye, C.; Chen, C.; Xiong, H.; Xie, B.; Zhou, J.; Chen, Y.; Zheng, S.; Wang, L. Glucose transporter GLUT1 expression and clinical outcome in solid tumors: a systematic review and meta-analysis. Oncotarget, 2017, 8(10), 16875-16886.
[http://dx.doi.org/10.18632/oncotarget.15171] [PMID: 28187435]
[11]
Wierstra, I. FOXM1 (Forkhead box M1) in tumorigenesis: overexpression in human cancer, implication in tumorigenesis, oncogenic functions, tumor-suppressive properties, and target of anticancer therapy. Adv. Cancer Res., 2013, 119, 191-419.
[http://dx.doi.org/10.1016/B978-0-12-407190-2.00016-2] [PMID: 23870513]
[12]
Halasi, M.; Gartel, A.L. FOX(M1) news--it is cancer. Mol. Cancer Ther., 2013, 12(3), 245-254.
[http://dx.doi.org/10.1158/1535-7163.MCT-12-0712] [PMID: 23443798]
[13]
Pilarsky, C.; Wenzig, M.; Specht, T.; Saeger, H.D.; Grützmann, R. Identification and validation of commonly overexpressed genes in solid tumors by comparison of microarray data. Neoplasia, 2004, 6(6), 744-750.
[http://dx.doi.org/10.1593/neo.04277] [PMID: 15720800]
[14]
Laoukili, J.; Stahl, M.; Medema, R.H. FoxM1: at the crossroads of ageing and cancer. Biochim. Biophys. Acta, 2007, 1775(1), 92-102.
[PMID: 17014965]
[15]
Bhat, U.G.; Jagadeeswaran, R.; Halasi, M.; Gartel, A.L. Nucleophosmin interacts with FOXM1 and modulates the level and localization of FOXM1 in human cancer cells. J. Biol. Chem., 2011, 286(48), 41425-41433.
[http://dx.doi.org/10.1074/jbc.M111.270843] [PMID: 21979956]
[16]
Cui, J.; Shi, M.; Xie, D.; Wei, D.; Jia, Z.; Zheng, S.; Gao, Y.; Huang, S.; Xie, K. FOXM1 promotes the warburg effect and pancreatic cancer progression via transactivation of LDHA expression. Clin. Cancer Res., 2014, 20(10), 2595-2606.
[17]
Caldwell, S.A.; Jackson, S.R.; Shahriari, K.S.; Lynch, T.P.; Sethi, G.; Walker, S.; Vosseller, K.; Reginato, M.J. Nutrient sensor O-GlcNAc transferase regulates breast cancer tumorigenesis through targeting of the oncogenic transcription factor FoxM1. Oncogene, 2010, 29(19), 2831-2842.
[http://dx.doi.org/10.1038/onc.2010.41] [PMID: 20190804]
[18]
Shang, R.; Pu, M.; Li, Y.; Wang, D. FOXM1 regulates glycolysis in hepatocellular carcinoma by transactivating glucose transporter 1 expression. Oncol. Rep., 2017, 37(4), 2261-2269.
[http://dx.doi.org/10.3892/or.2017.5472] [PMID: 28260073]
[19]
Wang, Y.; Yun, Y.; Wu, B.; Wen, L.; Wen, M.; Yang, H.; Zhao, L.; Liu, W.; Huang, S.; Wen, N.; Li, Y. FOXM1 promotes reprogramming of glucose metabolism in epithelial ovarian cancer cells via activation of GLUT1 and HK2 transcription. Oncotarget, 2016, 7(30), 47985-47997.
[http://dx.doi.org/10.18632/oncotarget.10103] [PMID: 27351131]
[20]
Strickaert, A.; Saiselet, M.; Dom, G.; De Deken, X.; Dumont, J.E.; Feron, O.; Sonveaux, P.; Maenhaut, C. Cancer heterogeneity is not compatible with one unique cancer cell metabolic map. Oncogene, 2017, 36(19), 2637-2642.
[http://dx.doi.org/10.1038/onc.2016.411] [PMID: 27797377]
[21]
Allen, A.E.; Locasale, J.W. Glucose metabolism in cancer: The saga of pyruvate kinase continues. Cancer Cell, 2018, 33(3), 337-339.
[http://dx.doi.org/10.1016/j.ccell.2018.02.008] [PMID: 29533776]
[22]
Jung, S.Y.; Sobel, E.M.; Papp, J.C.; Zhang, Z.F. Effect of genetic variants and traits related to glucose metabolism and their interaction with obesity on breast and colorectal cancer risk among postmenopausal women. BMC Cancer, 2017, 17(1), 290.
[http://dx.doi.org/10.1186/s12885-017-3284-7] [PMID: 28446149]
[23]
Xu, J.; Ye, Y.; Wu, H.; Duerksen-Hughes, P.; Zhang, H.; Li, P.; Huang, J.; Yang, J.; Wu, Y.; Xia, D. Association between markers of glucose metabolism and risk of colorectal cancer. BMJ Open, 2016, 6(6)e011430
[http://dx.doi.org/10.1136/bmjopen-2016-011430] [PMID: 27354075]
[24]
Yao, Z.; Xie, F.; Li, M.; Liang, Z.; Xu, W.; Yang, J.; Liu, C.; Li, H.; Zhou, H.; Qu, L.H. Oridonin induces autophagy via inhibition of glucose metabolism in p53-mutated colorectal cancer cells. Cell Death Dis., 2017, 8(2)e2633
[http://dx.doi.org/10.1038/cddis.2017.35] [PMID: 28230866]
[25]
Zhang, D.; Li, J.; Wang, F.; Hu, J.; Wang, S.; Sun, Y. 2-Deoxy-D-glucose targeting of glucose metabolism in cancer cells as a potential therapy. Cancer Lett., 2014, 355(2), 176-183.
[http://dx.doi.org/10.1016/j.canlet.2014.09.003] [PMID: 25218591]
[26]
Feng, W.; Cui, G.; Tang, C.W.; Zhang, X.L.; Dai, C.; Xu, Y.Q.; Gong, H.; Xue, T.; Guo, H.H.; Bao, Y. Role of glucose metabolism related gene GLUT1 in the occurrence and prognosis of colorectal cancer. Oncotarget, 2017, 8(34), 56850-56857.
[http://dx.doi.org/10.18632/oncotarget.18090] [PMID: 28915636]
[27]
GabAllah, G.M.K.; Habib, E-D M.S.; Soliman, S.E.; Kasemy, Z.A.; Gohar, S.F. Validity and clinical impact of glucose transporter 1 expression in colorectal cancer. Saudi J. Gastroenterol., 2017, 23(6), 348-356.
[28]
Wang, T.; Ning, K.; Lu, T.X.; Hua, D. Elevated expression of TrpC5 and GLUT1 is associated with chemoresistance in colorectal cancer. Oncol. Rep., 2017, 37(2), 1059-1065.
[http://dx.doi.org/10.3892/or.2016.5322] [PMID: 28000878]
[29]
Wu, X.L.; Wang, L.K.; Yang, D.D.; Qu, M.; Yang, Y.J.; Guo, F.; Han, L.; Xue, J. Effects of Glut1 gene silencing on proliferation, differentiation, and apoptosis of colorectal cancer cells by targeting the TGF-β/PI3K-AKT-mTOR signaling pathway. J. Cell. Biochem., 2018, 119(2), 2356-2367.
[http://dx.doi.org/10.1002/jcb.26399] [PMID: 28884839]
[30]
Laissue, P. The forkhead-box family of transcription factors: key molecular players in colorectal cancer pathogenesis. Mol. Cancer, 2019, 18(1), 5.
[http://dx.doi.org/10.1186/s12943-019-0938-x] [PMID: 30621735]
[31]
Escasa, S.R.; Harrison, R.L.; Mowery, J.D.; Bauchan, G.R.; Cory, J.S. The complete genome sequence of an alphabaculovirus from Spodoptera exempta, an agricultural pest of major economic significance in Africa. PLoS One, 2019, 14(2)e0209937
[http://dx.doi.org/10.1371/journal.pone.0209937] [PMID: 30735528]
[32]
Yao, G.; Zhang, Y.; Wang, D.; Yang, R.; Sang, H.; Han, L.; Zhu, Y.; Lu, Y.; Tan, Y.; Shang, Z. GDM-induced macrosomia is reversed by Cav-1 via AMPK-mediated fatty acid transport and GLUT1-mediated glucose transport in placenta. PLoS One, 2017, 12(1)e0170490
[http://dx.doi.org/10.1371/journal.pone.0170490] [PMID: 28125642]
[33]
Ho, C.; Wang, C.; Mattu, S.; Destefanis, G.; Ladu, S.; Delogu, S.; Armbruster, J.; Fan, L.; Lee, S.A.; Jiang, L.; Dombrowski, F.; Evert, M.; Chen, X.; Calvisi, D.F. AKT (v-akt murine thymoma viral oncogene homolog 1) and N-Ras (neuroblastoma ras viral oncogene homolog) coactivation in the mouse liver promotes rapid carcinogenesis by way of mTOR (mammalian target of rapamycin complex 1), FOXM1 (forkhead box M1)/SKP2, and c-Myc pathways. Hepatology, 2012, 55(3), 833-845.
[http://dx.doi.org/10.1002/hep.24736] [PMID: 21993994]
[34]
Tian, L.; Zhao, Z.; Xie, L.; Zhu, J. MiR-361-5p suppresses chemoresistance of gastric cancer cells by targeting FOXM1 via the PI3K/Akt/mTOR pathway. Oncotarget, 2017, 9(4), 4886-4896.
[PMID: 29435149]
[35]
Chu, X.Y.; Zhu, Z.M.; Chen, L.B.; Wang, J.H.; Su, Q.S.; Yang, J.R.; Lin, Y.; Xue, L.J.; Liu, X.B.; Mo, X.B. FOXM1 expression correlates with tumor invasion and a poor prognosis of colorectal cancer. Acta Histochem., 2012, 114(8), 755-762.
[http://dx.doi.org/10.1016/j.acthis.2012.01.002] [PMID: 22326401]
[36]
Weng, W.; Okugawa, Y.; Toden, S.; Toiyama, Y.; Kusunoki, M.; Goel, A. FOXM1 and FOXQ1 are promising prognostic biomarkers and novel targets of tumor-suppressive miR-342 in human colorectal cancer. Clin. Cancer Res., 2016, 22(19), 4947-4957.
[PMID: 27162244]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 20
ISSUE: 8
Year: 2020
Published on: 24 July, 2020
Page: [941 - 950]
Pages: 10
DOI: 10.2174/1871520620666200318094618
Price: $65

Article Metrics

PDF: 26
HTML: 3