果糖-1,6-二磷酸酶与肿瘤代谢
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摘要
代谢重编程已被定义为肿瘤细胞的标志性特征之一。果糖-1,6-二磷酸酶1(fructose-1,6-bisphosphatase 1,FBP1是糖异生的限速酶,其在多种类型肿瘤组织中的表达均下调,可能的机制为DNA甲基化,转录因子、微小RNA及蛋白泛素化调控等。FBP1低表达与癌症低生存率和高复发率相关。FBP1抑制Warburg效应以及Wnt/β-Catenin、缺氧诱导因子(hypoxia-inducible factor,HIF)及RAS/MAK等信号通路,从而抑制肿瘤进展。同时,FBP1在NK细胞的免疫杀伤过程中也发挥作用。但FBP1在癌症进展中的作用仍有众多问题需要研究。
Metabolic reprogramming has been de?ned as a hallmark of cancer cells. Fructose-1,6-phosphatase 1(FBP1) is a ratelimiting enzyme for gluconeogenesis. FBP1 is generally down-regulated in various types of tumor tissues. The down-regulation of FBP1 is driven by multiple mechanisms, including DNA promoter methylation, transcription factor, microRNA and protein ubiquitination-mediated regulation. Low levels of FBP1 are associated with short patient survival and high recurrence rates. FBP1 inhibits the Warburg effect and multiple protumorigenic signaling pathways, including Wnt/β-Catenin, hypoxia-inducible factor(HIF),RAS/MAK, to inhibit tumor progression. Moreover, FBP1 also plays a role in modulating tumor immunity mediated by NK cells.However, many remaining questions about the role of FBP1 in cancer demand further efforts.
Metabolic reprogramming has been de?ned as a hallmark of cancer cells. Fructose-1,6-phosphatase 1(FBP1) is a ratelimiting enzyme for gluconeogenesis. FBP1 is generally down-regulated in various types of tumor tissues. The down-regulation of FBP1 is driven by multiple mechanisms, including DNA promoter methylation, transcription factor, microRNA and protein ubiquitination-mediated regulation. Low levels of FBP1 are associated with short patient survival and high recurrence rates. FBP1 inhibits the Warburg effect and multiple protumorigenic signaling pathways, including Wnt/β-Catenin, hypoxia-inducible factor(HIF),RAS/MAK, to inhibit tumor progression. Moreover, FBP1 also plays a role in modulating tumor immunity mediated by NK cells.However, many remaining questions about the role of FBP1 in cancer demand further efforts.
引文
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[16]Liu X,Wang X,Zhang J,et al.Warburg effect revisited:an epig enetic link between glycolysis and gastric carcino genesis[J].Oncogene,2010,29(3):442-450.
[17]Li Q,Wei P,Wu J,et al.The FOXC1/FBP1 signaling axis promotes colorectal cancer proliferation by enhancing the Warb urg effect[J].Oncogene,2019,38(4):483-496.
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[19]Chen LY,Cheng CS,Qu C,et al.CBX3 promotes proliferation and regulates glycolysis via suppressing FBP1 in pancreatic cancer[J].Biochem Biophys Res Commun,2018,500(3):691-697.
[20]Xiong X,Zhang J,Hua X,et al.FBP1 promotes ovarian cancer development through the acceleration of cell cycle transition and metastasis[J].Oncol Lett,2018,16(2):1682-1688.
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[25]Dong C,Yuan T,Wu Y,et al.Loss of FBP1 by Snail-mediated repression provides metabolic advantages in basal-like breast cancer[J].Cancer Cell,2013,23(3):316-331.
[26]Liu Y,Jiang Y,Wang N,et al.Invalidation of mitophagy by FBP1-mediated repression promotes apoptosis in breast cancer[J].Tumour Biol,2017,39(6):1010428317708779.
[27]Barcena-Varela M,Caruso S,Llerena S,et al.Dual Targeting of Histone Methyltransferase G9a and DNA-Methyltransferase 1for the Treatment of Experimental Hepatocellular Carcinoma[J].Hepatology,2019,69(2):587-603.
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[29]Zhang D,Li Z,Li T,et al.miR-517a promotes Warburg effect in HCC by directly targeting FBP1[J].Onco Targets Ther,2018,11:8025-8032.
[30]Dai Q,Li N,Zhou X.Increased miR-21a provides metabolic advantages through suppression of FBP1 expression in nonsmall cell lung cancer cells[J].Am J Cancer Res,2017,7(11):2121-2130.
[31]Jin X,Pan Y,Wang L,et al.MAGE-TRIM28 complex promotes the Warburg effect and hepatocellular carcinoma progression by targeting FBP1 for degradation[J].Oncogenesis,2017,6(4):e312.
[32]Herzog B,Waltner-Law M,Scott DK,et al.Characterization of the human liver fructose-1,6-bisphosphatase gene promoter[J].Biochem J,2000,351 Pt 2:385-392.
[33]Deberardinis RJ,Lum JJ,Hatzivassiliou G,et al.The biology of cancer:metabolic reprogramming fuels cell growth and prolif eration[J].Cell Metab,2008,7(1):11-20.
[34]Han B,Bhowmick N,Qu Y,et al.FOXC1:an emerging marker and therapeutic target for cancer[J].Oncogene,2017,36(28):3957-3963.
[35]Cairns RA,Harris IS,Mak TW.Regulation of cancer cell metabolism[J].Nat Rev Cancer,2011,11(2):85-95.
[36]Jin X,Pan Y,Wang L,et al.Fructose-1,6-bisphosphatase Inhibits ERK Activation and Bypasses Gemcitabine Resistance in Pancreatic Cancer by Blocking IQGAP1-MAPKInteraction[J].Cancer Res,2017,77(16):4328-4341.
[37]Vivier E,Tomasello E,Baratin M,et al.Functions of natural killer cells[J].Nat Immunol,2008,9(5):503-510.
[38]Malmberg KJ,Carlsten M,Bjorklund A,et al.Natural killer cell-mediated immunosurveillance of human cancer[J].Semin Immunol,2017,31:20-29.
[39]Smyth MJ,Hayakawa Y,Takeda K,et al.New aspects of natural-killer-cell surveillance and therapy of cancer[J].Nat Rev Cancer,2002,2(11):850-861.
[40]Cong J,Wang X,Zheng X,et al.Dysfunction of Natural Killer Cells by FBP1-Induced Inhibition of Glycolysis during Lung Cancer Progression[J].Cell Metab,2018,28(2):243-255.
[41]Mamczur P,Sok AJ,Rzechonek A,et al.Cell cycle-dependent expression and subcellular localization of fructose 1,6-bisphosphatase[J].Histochem Cell Biol,2012,137(1):121-136.
[2]Vander Heiden MG,Cantley LC,Thompson CB.Understanding the Warburg effect:the metabolic requirements of cell proliferation[J].Science,2009,324(5930):1029-1033.
[3]Yizhak K,Chaneton B,Gottlieb E,et al.Modeling cancer metabo lism on a genome scale[J].Mol Syst Biol,2015,11(6):817.
[4]Liang JY,Huang S,Zhang Y,et al.Crystal structure of the neutral form of fructose 1,6-bisphosphatase complexed with regulatory inhibitor fructose 2,6-bisphosphate at 2.6-A resolution[J].Proc Natl Acad Sci U S A,1992,89(6):2404-2408.
[5]Ward PS,Thompson CB.Metabolic reprogramming:a cancer hallmark even warburg did not anticipate[J].Cancer Cell,2012,21(3):297-308.
[6]Pogell BM,Mc GR.Partial purification of fructose-1,6-diphosphatase[J].J Biol Chem,1954,208(1):149-157.
[7]Chen M,Zhang J,Li N,et al.Promoter hypermethylation mediated downregulation of FBP1 in human hepatocellular carcinoma and colon cancer[J].PLoS One,2011,6(10):e25564.
[8]Hirata H,Sugimachi K,Komatsu H,et al.Decreased Expression of Fructose-1,6-bisphosphatase Associates with Glucose Metabolism and Tumor Progression in Hepatocellular Carcinoma[J].Cancer Res,2016,76(11):3265-3276.
[9]Li B,Qiu B,Lee DS,et al.Fructose-1,6-bisphosphatase opposes renal carcinoma progression[J].Nature,2014,513(7517):251-255.
[10]Li H,Wang J,Xu H,et al.Decreased fructose-1,6-bisphosphatase-2 expression promotes glycolysis and growth in gastric cancer cells[J].Mol Cancer,2013,12(1):110.
[11]Li K,Ying M,Feng D,et al.Fructose-1,6-bisphosphatase is a novel regulator of Wnt/beta-Catenin pathway in breast cancer[J].Biomed Pharmacother,2016,84:1144-1149.
[12]Ning XH,Li T,Gong YQ,et al.Association between FBP1and hypoxia-related gene expression in clear cell renal cell carcinoma[J].Oncol Lett,2016,11(6):4095-4098.
[13]Yang J,Wang C,Zhao F,et al.Loss of FBP1 facilitates aggressive features of hepatocellular carcinoma cells through the Warburg effect[J].Carcinogenesis,2017,38(2):134-143.
[14]Zhang J,Wang J,Xing H,et al.Down-regulation of FBP1 by ZEB1-mediated repression confers to growth and invasion in lung cancer cells[J].Mol Cell Biochem,2016,411(1-2):331-340.
[15]Liu Z,Ma Y,Yang J,et al.Upregulated and downregulated proteins in hepatocellular carcinoma:a systematic review of proteomic profiling studies[J].OMICS,2011,15(1-2):61-71.
[16]Liu X,Wang X,Zhang J,et al.Warburg effect revisited:an epig enetic link between glycolysis and gastric carcino genesis[J].Oncogene,2010,29(3):442-450.
[17]Li Q,Wei P,Wu J,et al.The FOXC1/FBP1 signaling axis promotes colorectal cancer proliferation by enhancing the Warb urg effect[J].Oncogene,2019,38(4):483-496.
[18]Wang B,Fan P,Zhao J,et al.FBP1 loss contributes to BETinhibitors resistance by undermining c-Myc expression in pancreatic ductal adenocarcinoma[J].J Exp Clin Cancer Res,2018,37(1):224.
[19]Chen LY,Cheng CS,Qu C,et al.CBX3 promotes proliferation and regulates glycolysis via suppressing FBP1 in pancreatic cancer[J].Biochem Biophys Res Commun,2018,500(3):691-697.
[20]Xiong X,Zhang J,Hua X,et al.FBP1 promotes ovarian cancer development through the acceleration of cell cycle transition and metastasis[J].Oncol Lett,2018,16(2):1682-1688.
[21]Zhao W,Yang S,Chen J,et al.Forced overexpression of FBP1inhibits proliferation and metastasis in cholangiocarcinoma cells via Wnt/beta-catenin pathway[J].Life Sci,2018,210:224-234.
[22]Alderton GK.Tumorigenesis:FBP1 is suppressed in kidney tumours[J].Nat Rev Cancer,2014,14(9):575.
[23]Chen J,Lee HJ,Wu X,et al.Gain of glucose-independent growth upon metastasis of breast cancer cells to the brain[J].Cancer Res,2015,75(3):554-565.
[24]Zhu Y,Shi M,Chen H,et al.NPM1 activates metabolic changes by inhibiting FBP1 while promoting the tumorigenicity of pancreatic cancer cells[J].Oncotarget,2015,6(25):21443-21451.
[25]Dong C,Yuan T,Wu Y,et al.Loss of FBP1 by Snail-mediated repression provides metabolic advantages in basal-like breast cancer[J].Cancer Cell,2013,23(3):316-331.
[26]Liu Y,Jiang Y,Wang N,et al.Invalidation of mitophagy by FBP1-mediated repression promotes apoptosis in breast cancer[J].Tumour Biol,2017,39(6):1010428317708779.
[27]Barcena-Varela M,Caruso S,Llerena S,et al.Dual Targeting of Histone Methyltransferase G9a and DNA-Methyltransferase 1for the Treatment of Experimental Hepatocellular Carcinoma[J].Hepatology,2019,69(2):587-603.
[28]Wattanavanitchakorn S,Rojvirat P,Chavalit T,et al.CCAAT-enhancer binding protein-alpha(C/EBPalpha)and hepatocyte nuclear factor 4alpha(HNF4alpha)regulate expression of the human fructose-1,6-bisphosphatase 1(FBP1)gene in human hepatocellular carcinoma HepG2 cells[J].PLoS One,2018,13(3):e0194252.
[29]Zhang D,Li Z,Li T,et al.miR-517a promotes Warburg effect in HCC by directly targeting FBP1[J].Onco Targets Ther,2018,11:8025-8032.
[30]Dai Q,Li N,Zhou X.Increased miR-21a provides metabolic advantages through suppression of FBP1 expression in nonsmall cell lung cancer cells[J].Am J Cancer Res,2017,7(11):2121-2130.
[31]Jin X,Pan Y,Wang L,et al.MAGE-TRIM28 complex promotes the Warburg effect and hepatocellular carcinoma progression by targeting FBP1 for degradation[J].Oncogenesis,2017,6(4):e312.
[32]Herzog B,Waltner-Law M,Scott DK,et al.Characterization of the human liver fructose-1,6-bisphosphatase gene promoter[J].Biochem J,2000,351 Pt 2:385-392.
[33]Deberardinis RJ,Lum JJ,Hatzivassiliou G,et al.The biology of cancer:metabolic reprogramming fuels cell growth and prolif eration[J].Cell Metab,2008,7(1):11-20.
[34]Han B,Bhowmick N,Qu Y,et al.FOXC1:an emerging marker and therapeutic target for cancer[J].Oncogene,2017,36(28):3957-3963.
[35]Cairns RA,Harris IS,Mak TW.Regulation of cancer cell metabolism[J].Nat Rev Cancer,2011,11(2):85-95.
[36]Jin X,Pan Y,Wang L,et al.Fructose-1,6-bisphosphatase Inhibits ERK Activation and Bypasses Gemcitabine Resistance in Pancreatic Cancer by Blocking IQGAP1-MAPKInteraction[J].Cancer Res,2017,77(16):4328-4341.
[37]Vivier E,Tomasello E,Baratin M,et al.Functions of natural killer cells[J].Nat Immunol,2008,9(5):503-510.
[38]Malmberg KJ,Carlsten M,Bjorklund A,et al.Natural killer cell-mediated immunosurveillance of human cancer[J].Semin Immunol,2017,31:20-29.
[39]Smyth MJ,Hayakawa Y,Takeda K,et al.New aspects of natural-killer-cell surveillance and therapy of cancer[J].Nat Rev Cancer,2002,2(11):850-861.
[40]Cong J,Wang X,Zheng X,et al.Dysfunction of Natural Killer Cells by FBP1-Induced Inhibition of Glycolysis during Lung Cancer Progression[J].Cell Metab,2018,28(2):243-255.
[41]Mamczur P,Sok AJ,Rzechonek A,et al.Cell cycle-dependent expression and subcellular localization of fructose 1,6-bisphosphatase[J].Histochem Cell Biol,2012,137(1):121-136.