磷酸甘油酸激酶1与肿瘤
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摘要
磷酸甘油酸激酶1 (PGK1)是糖酵解过程中一个重要的催化酶,催化1,3-二磷酸甘油酸转变成3-磷酸甘油酸,产生一分子ATP。研究表明, PGK1在多种肿瘤中高表达,既可以作为蛋白激酶也可以作为代谢酶,通过影响肿瘤的代谢而影响肿瘤的发生发展过程,还与多种肿瘤患者的放化疗抵抗和预后不良有关。本文就其功能及与肿瘤的关系进行综述,旨在为靶向PGK1进行药物开发提供理论基础。
Phosphoglycerate kinase 1(PGK1) is a key metabolic enzyme in the glycolysis pathway, which catalyzes the transfer of 1, 3-bisphosphoglycerate(1, 3-BPG) to 3-phosphoglycerate(3-PG) with ATP production.Over-expression of PGK1 has been observed in many types of malignance. Besides as a metabolic enzyme, PGK1 can also act as a protein kinase, which promotes the development and progression of tumors and correlates with chemoradiotherapy resistance and poor survival of cancer patients by regulating tumor cell metabolism. Functions of PGK1 were summarized in this article to provide theoretical basis for PGK1-targeting drug development.
Phosphoglycerate kinase 1(PGK1) is a key metabolic enzyme in the glycolysis pathway, which catalyzes the transfer of 1, 3-bisphosphoglycerate(1, 3-BPG) to 3-phosphoglycerate(3-PG) with ATP production.Over-expression of PGK1 has been observed in many types of malignance. Besides as a metabolic enzyme, PGK1 can also act as a protein kinase, which promotes the development and progression of tumors and correlates with chemoradiotherapy resistance and poor survival of cancer patients by regulating tumor cell metabolism. Functions of PGK1 were summarized in this article to provide theoretical basis for PGK1-targeting drug development.
引文
[1] Wu D, Wu ZD, Yu XB. Advance in the research of phosphoglycerate kinase[J]. China Trop Med(中国热带医学),2005,5:375-378.
[2] Fiorillo A, Petrosino M, Ilari A, et al. The phosphoglycerate kinase 1 variants found in carcinoma cells display different catalytic activity and conformational stability compared to the native enzyme[J]. PLoS One, 2018, 13:e0199191.
[3] Zerrad L, Merli A, Schroder G, et al. A spring-loaded release mechanism regulates domain movement and catalysis in phosphoglycerate kinase[J]. J Biol Chem, 2011, 286:14040-14048.
[4] Li XL. Structural Study of Human Lymphocyte Antigen B*5801and Structural Study of Complex of Phosphoglycerate Kinase with Terazosin(人白细胞抗原分子B*5801结构研究及磷酸甘油酸激酶与特拉唑嗪复合物结构研究)[D]. Heifei:University of Science and Technology of China, 2016.
[5] Lu ZM, Hunter T. Metabolic kinases moonlighting as protein kinases[J]. Trends Biochem Sci, 2018, 43:301-310.
[6] Hu H, Zhu W, Qin J, et al. Acetylation of PGK1 promotes liver cancer cell proliferation and tumorigenesis[J]. Hepatology,2017, 65:515-528.
[7] Ai J, Huang H, Lv X, et al. FLNA and PGK1 are two potential markers for progression in hepatocellular carcinoma[J]. Cell Physiol Biochem, 2011, 27:207-216.
[8] Ahmad S, Glatzle J, Bajaeifer K, et al. Phosphoglycerate kinase1 as a promoter of metastasis in colon cancer[J]. Int J Oncol2013,43:586-590.
[9] Hwang T, Liang Y, Chien K, et al. Overexpression and elevated serum levels of phosphoglycerate kinase 1 in pancreatic ductal adenocarcinoma[J]. Proteomics, 2006, 6:2259-2272.
[10] Zhang NW. Study on the Role and the Related Mechanism of PGK1 and Its Lysine Succinylation Midification in Renal Cell Carcinoma(PGKl及其赖氨酸琥珀酰化修饰在肾细胞痛癌中的作用及其相关机制研究)[D]. Shenyang:China Medical University, 2018.
[11] Gao HJ, Zhou YP, Mao YS, et al. Phosphoglycerate kinase 1 as a candidate of tumor associated antigen identified from esophageal squamous cell carcinoma[J]. World Chin J Digestol(世界华人消化杂志),2008, 16:1866-1872.
[12] Lin L, Jiang QP, Lin D, et al. Expression of phosphoglycerate kinase 1 in endometrial carcinoma and its association with patients'outcome[J]. J South Med Univ(南方医科大学学报),2018,38:471-476.
[13] Li X, Jiang Y, Meisenhelder J, et al. Mitochondria-translocated PGK1 functions as a protein kinase to coordinate glycolysis and the TCA cycle in tumorigenesis[J]. Mol Cell, 2016, 61:705-719.
[14] Zhang Y, Yu G, Chu H, et al. Macrophage-associated PGK1phosphorylation promotes aerobic glycolysis and tumorigenesis[J]. Mol Cell, 2018,71:201-215.
[15] Wang GZ, Qi X, Li J. Eukaryotic elongation factor 2 kinase and cancer[J]. Acta Pharm Sin(药学学报),2015, 50:808-813.
[16] Qian X, Li X, Cai Q, et al. Phosphoglycerate kinase 1 phosphorylates Beclinl to induce autophagy[J]. Mol Cell, 2017, 65:917-931.e6
[17] Ying P, Yang C, Schovanek J, et al. Anthracyclines suppress pheochromocytoma cell characteristics, including metastasis,through inhibition of the hypoxia signaling pathway[J]. Oncotarget, 2017,8:22313-22324.
[18] Tang SW, Chang WH, Su YT, et al. MYC pathway is activated in clear cell renal cell carcinoma and essential for proliferation of clear cell renal cell carcinoma cells[J]. Cancer Lett, 2009, 273:35-43.
[19] Shashni B, Sakharkar K, Nagasaki Y, et al. Glycolytic enzymes PGK1 and PKM2 as novel transcriptional targets of PPAR gamma in breast cancer pathophysiology[J]. J Drug Target,2013,21:161-174.
[20] Xu D, Aka J, Wang R, et al. 17β-Hydroxysteroid dehydrogenase type 5 is negatively correlated to apoptosis inhibitor GRP78 and tumor-secreted protein PGK1, and modulates breast cancer cell viability and proliferation[J]. J Steroid Biochem Mol Biol, 2017,171:270-280.
[21] Wang J, Ying G, Wang J, et al. Characterization of phosphoglycerate kinase-1 expression of stromal cells derived from tumor microenvironment in prostate cancer progression[J]. CancerRes, 2010, 70:471-480.
[22] Wang J, Wang J, Dai J, et al. A glycolytic mechanism regulating an angiogenic switch in prostate cancer[J]. Cancer Res, 2007,67:149-159.
[23] Ameis H, Drenckhan A, Loga KV, et al. PGK1 as predictor of CXCR4 expression, bone marrow metastases and survival in neuroblastoma[J]. PLoS One, 2013, 8:e83701.
[24] Jung Y, Shiozawa Y, Wang J, et al. Expression of PGK1 by prostate cancer cells induces bone formation[J]. Mol Cancer Res, 2009,7:1595-1604.
[25] Yu T, Zhao Y, Hu Z, et al. MetaLnc9 facilitates lung cancer metastasis via a PGK1-activated AKT/mTOR pathway[J].Cancer Res,2017, 77:5782-5794.
[26] Jing C, Cao S,Bo S, et al. Metabolic reprogramming-based characterization of circulating tumor cells in prostate cancer[J].J Exp Clin Cancer Res, 2018, 37:127-142.
[27] Zieker D, Koenigsrainer I, Traub F,et al. PGK1 a potential marker for peritoneal dissemination in gastric cancer[J]. Cell Physiol Biochem, 2008, 21:429-436.
[28] Zieker D, Koenigsrainer K, Tritschler I, et al. Phosphoglycerate kinase 1 a promoting enzyme for peritoneal dissemination in gastric cancer[J]. Int J Cancer, 2010, 126:1513-1520.
[29] Zieker D, Koenigsrainer I, Weinreich J, et al. Phosphoglycerate kinase 1 promoting tumor progression and metastasis in gastric cancer-detected in a tumor mouse model using positron emission tomography/magnetic resonance imaging[J]. Cell Physiol Biochem, 2010, 26:147-154.
[30] Xie H, Tong G, Zhang Y, et al. PGK1 drives hepatocellular carcinoma metastasis by enhancing metabolic process[J]. Int J Mol Sci, 2017, 18:1630-1641.
[31] Schneider CC, Archid R, Fischer N, et al. Metabolic alterationovercoming therapy resistance in gastric cancer via PGK-1 inhibition in a combined therapy with standard chemotherapeutics[J]. Int J Surgery, 2015, 22:92-98.
[32] Lepleux C, Abeilard-Lemoisson E, Duval M, et al. siPGKl sensitizes chemoresistant human ovarian cancer cell lines to cisplatin[J]. Anticancer Res, 2012, 32:4277-4286.
[33] Sun S, Liang X, Zhang X, et al. Phosphoglycerate kinase-1 is a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in breast cancer[J]. Br J Cancer, 2015, 112:1332-1339.
[34] Yan H, Yang K, Xiao H, et al. Over-expression of cofilin-1and phosphoglycerate kinase 1 in astrocytomas involved in pathogenesis of radioresistance[J]. CNS Neurosci Ther, 2012,18:729-736.
[35] Sun WB. The Relationship between CFL1 and PGK1 and Radiosensitivity and Prognosis of Human Glioma(CFLl和PGK1与人脑胶质细胞瘤放射敏感性及预后的关系研究)[D]. Nanjing:Nanjing Medical University, 2018.
[36] Chen G, Gharib T, Wang H, et al. Protein profiles associatedwith survival in lung adenocarcinoma[J]. Proc Natl Acad Sci USA, 2003, 100:13537-13542.
[37] Yuan SX. The Role and Clinical Significance of Long Noncoding RNA in Hepatocellular Carcinoma(长链非编码RNA在肝癌发生、发展过程中的作用及临床意义)[D]. Shanghai:The Second Military Medical University, 2014.
[38] Ho MY, Tang SJ, Ng WV, et al. Nucleotide-binding domain of phosphoglycerate kinase 1 reduces tumor growth by suppressing COX-2 expression[J]. Cancer Sci, 2010, 10:2411-2416.
[39] Tang SJ, Ho MY, Cho HC, et al. Phosphoglycerate kinase 1-over-expressing lung cancer cells reduce cyclooxygenase 2 expression and promote anti-tumor immunity in vivo[J]. Int J Cancer, 2008,123:2840-2848.
[40] Lu W, Gao J, Yang J, et al. Down-regulated phosphoglycerate kinase 1 expression is associated with poor prognosis in patients with gallbladder cancer[J]. Medicine, 2015, 94:e2244.
[41] Shichijo S, Azuma K, Komatsu N, et al. Two proliferationrelated proteins, TYMS and PGK1, could be new cytotoxic T lymphocyte-directed tumor-associated antigens of HLA-A2+colon cancer[J]. Clin Cancer Res, 2004, 10:5828-5836.
[2] Fiorillo A, Petrosino M, Ilari A, et al. The phosphoglycerate kinase 1 variants found in carcinoma cells display different catalytic activity and conformational stability compared to the native enzyme[J]. PLoS One, 2018, 13:e0199191.
[3] Zerrad L, Merli A, Schroder G, et al. A spring-loaded release mechanism regulates domain movement and catalysis in phosphoglycerate kinase[J]. J Biol Chem, 2011, 286:14040-14048.
[4] Li XL. Structural Study of Human Lymphocyte Antigen B*5801and Structural Study of Complex of Phosphoglycerate Kinase with Terazosin(人白细胞抗原分子B*5801结构研究及磷酸甘油酸激酶与特拉唑嗪复合物结构研究)[D]. Heifei:University of Science and Technology of China, 2016.
[5] Lu ZM, Hunter T. Metabolic kinases moonlighting as protein kinases[J]. Trends Biochem Sci, 2018, 43:301-310.
[6] Hu H, Zhu W, Qin J, et al. Acetylation of PGK1 promotes liver cancer cell proliferation and tumorigenesis[J]. Hepatology,2017, 65:515-528.
[7] Ai J, Huang H, Lv X, et al. FLNA and PGK1 are two potential markers for progression in hepatocellular carcinoma[J]. Cell Physiol Biochem, 2011, 27:207-216.
[8] Ahmad S, Glatzle J, Bajaeifer K, et al. Phosphoglycerate kinase1 as a promoter of metastasis in colon cancer[J]. Int J Oncol2013,43:586-590.
[9] Hwang T, Liang Y, Chien K, et al. Overexpression and elevated serum levels of phosphoglycerate kinase 1 in pancreatic ductal adenocarcinoma[J]. Proteomics, 2006, 6:2259-2272.
[10] Zhang NW. Study on the Role and the Related Mechanism of PGK1 and Its Lysine Succinylation Midification in Renal Cell Carcinoma(PGKl及其赖氨酸琥珀酰化修饰在肾细胞痛癌中的作用及其相关机制研究)[D]. Shenyang:China Medical University, 2018.
[11] Gao HJ, Zhou YP, Mao YS, et al. Phosphoglycerate kinase 1 as a candidate of tumor associated antigen identified from esophageal squamous cell carcinoma[J]. World Chin J Digestol(世界华人消化杂志),2008, 16:1866-1872.
[12] Lin L, Jiang QP, Lin D, et al. Expression of phosphoglycerate kinase 1 in endometrial carcinoma and its association with patients'outcome[J]. J South Med Univ(南方医科大学学报),2018,38:471-476.
[13] Li X, Jiang Y, Meisenhelder J, et al. Mitochondria-translocated PGK1 functions as a protein kinase to coordinate glycolysis and the TCA cycle in tumorigenesis[J]. Mol Cell, 2016, 61:705-719.
[14] Zhang Y, Yu G, Chu H, et al. Macrophage-associated PGK1phosphorylation promotes aerobic glycolysis and tumorigenesis[J]. Mol Cell, 2018,71:201-215.
[15] Wang GZ, Qi X, Li J. Eukaryotic elongation factor 2 kinase and cancer[J]. Acta Pharm Sin(药学学报),2015, 50:808-813.
[16] Qian X, Li X, Cai Q, et al. Phosphoglycerate kinase 1 phosphorylates Beclinl to induce autophagy[J]. Mol Cell, 2017, 65:917-931.e6
[17] Ying P, Yang C, Schovanek J, et al. Anthracyclines suppress pheochromocytoma cell characteristics, including metastasis,through inhibition of the hypoxia signaling pathway[J]. Oncotarget, 2017,8:22313-22324.
[18] Tang SW, Chang WH, Su YT, et al. MYC pathway is activated in clear cell renal cell carcinoma and essential for proliferation of clear cell renal cell carcinoma cells[J]. Cancer Lett, 2009, 273:35-43.
[19] Shashni B, Sakharkar K, Nagasaki Y, et al. Glycolytic enzymes PGK1 and PKM2 as novel transcriptional targets of PPAR gamma in breast cancer pathophysiology[J]. J Drug Target,2013,21:161-174.
[20] Xu D, Aka J, Wang R, et al. 17β-Hydroxysteroid dehydrogenase type 5 is negatively correlated to apoptosis inhibitor GRP78 and tumor-secreted protein PGK1, and modulates breast cancer cell viability and proliferation[J]. J Steroid Biochem Mol Biol, 2017,171:270-280.
[21] Wang J, Ying G, Wang J, et al. Characterization of phosphoglycerate kinase-1 expression of stromal cells derived from tumor microenvironment in prostate cancer progression[J]. CancerRes, 2010, 70:471-480.
[22] Wang J, Wang J, Dai J, et al. A glycolytic mechanism regulating an angiogenic switch in prostate cancer[J]. Cancer Res, 2007,67:149-159.
[23] Ameis H, Drenckhan A, Loga KV, et al. PGK1 as predictor of CXCR4 expression, bone marrow metastases and survival in neuroblastoma[J]. PLoS One, 2013, 8:e83701.
[24] Jung Y, Shiozawa Y, Wang J, et al. Expression of PGK1 by prostate cancer cells induces bone formation[J]. Mol Cancer Res, 2009,7:1595-1604.
[25] Yu T, Zhao Y, Hu Z, et al. MetaLnc9 facilitates lung cancer metastasis via a PGK1-activated AKT/mTOR pathway[J].Cancer Res,2017, 77:5782-5794.
[26] Jing C, Cao S,Bo S, et al. Metabolic reprogramming-based characterization of circulating tumor cells in prostate cancer[J].J Exp Clin Cancer Res, 2018, 37:127-142.
[27] Zieker D, Koenigsrainer I, Traub F,et al. PGK1 a potential marker for peritoneal dissemination in gastric cancer[J]. Cell Physiol Biochem, 2008, 21:429-436.
[28] Zieker D, Koenigsrainer K, Tritschler I, et al. Phosphoglycerate kinase 1 a promoting enzyme for peritoneal dissemination in gastric cancer[J]. Int J Cancer, 2010, 126:1513-1520.
[29] Zieker D, Koenigsrainer I, Weinreich J, et al. Phosphoglycerate kinase 1 promoting tumor progression and metastasis in gastric cancer-detected in a tumor mouse model using positron emission tomography/magnetic resonance imaging[J]. Cell Physiol Biochem, 2010, 26:147-154.
[30] Xie H, Tong G, Zhang Y, et al. PGK1 drives hepatocellular carcinoma metastasis by enhancing metabolic process[J]. Int J Mol Sci, 2017, 18:1630-1641.
[31] Schneider CC, Archid R, Fischer N, et al. Metabolic alterationovercoming therapy resistance in gastric cancer via PGK-1 inhibition in a combined therapy with standard chemotherapeutics[J]. Int J Surgery, 2015, 22:92-98.
[32] Lepleux C, Abeilard-Lemoisson E, Duval M, et al. siPGKl sensitizes chemoresistant human ovarian cancer cell lines to cisplatin[J]. Anticancer Res, 2012, 32:4277-4286.
[33] Sun S, Liang X, Zhang X, et al. Phosphoglycerate kinase-1 is a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in breast cancer[J]. Br J Cancer, 2015, 112:1332-1339.
[34] Yan H, Yang K, Xiao H, et al. Over-expression of cofilin-1and phosphoglycerate kinase 1 in astrocytomas involved in pathogenesis of radioresistance[J]. CNS Neurosci Ther, 2012,18:729-736.
[35] Sun WB. The Relationship between CFL1 and PGK1 and Radiosensitivity and Prognosis of Human Glioma(CFLl和PGK1与人脑胶质细胞瘤放射敏感性及预后的关系研究)[D]. Nanjing:Nanjing Medical University, 2018.
[36] Chen G, Gharib T, Wang H, et al. Protein profiles associatedwith survival in lung adenocarcinoma[J]. Proc Natl Acad Sci USA, 2003, 100:13537-13542.
[37] Yuan SX. The Role and Clinical Significance of Long Noncoding RNA in Hepatocellular Carcinoma(长链非编码RNA在肝癌发生、发展过程中的作用及临床意义)[D]. Shanghai:The Second Military Medical University, 2014.
[38] Ho MY, Tang SJ, Ng WV, et al. Nucleotide-binding domain of phosphoglycerate kinase 1 reduces tumor growth by suppressing COX-2 expression[J]. Cancer Sci, 2010, 10:2411-2416.
[39] Tang SJ, Ho MY, Cho HC, et al. Phosphoglycerate kinase 1-over-expressing lung cancer cells reduce cyclooxygenase 2 expression and promote anti-tumor immunity in vivo[J]. Int J Cancer, 2008,123:2840-2848.
[40] Lu W, Gao J, Yang J, et al. Down-regulated phosphoglycerate kinase 1 expression is associated with poor prognosis in patients with gallbladder cancer[J]. Medicine, 2015, 94:e2244.
[41] Shichijo S, Azuma K, Komatsu N, et al. Two proliferationrelated proteins, TYMS and PGK1, could be new cytotoxic T lymphocyte-directed tumor-associated antigens of HLA-A2+colon cancer[J]. Clin Cancer Res, 2004, 10:5828-5836.