PKM2和Notch1在结直肠癌中的研究进展
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摘要
研究表明, M2型丙酮酸激酶(pyruvate kinase M2, PKM2)和Notch1在结直肠癌组织中高表达,且与结直肠癌的发生、发展有一定的关系;其表达水平亦与肿瘤的化、放疗效果有关,严重影响患者预后,是目前结直肠癌治疗和研究的关键靶点。PKM2主要通过调节癌细胞代谢及基因转录,促进癌细胞外泌体分泌,并在某些lncRNAs的调节下发挥促癌作用,可作为结直肠癌的辅助诊断指标。Notch1可在mi RNAs以及自噬的调节下发挥促癌作用,且可通过促进上皮间质转化(epithelial-mesenchymal transition, EMT)促进结直肠癌转移。此外,PKM2和Notch1在结直肠癌中的作用与Wnt/β-连环蛋白(β-catenin)信号通路有联系,但两者之间是否有相关性,目前尚不明确。本文主要就PKM2和Notch1在结直肠癌中的研究进展进行探讨,以期为结直肠癌的靶向治疗研究提供新思路。
Studies have shown that pyruvate kinase M2(PKM2) and Notch1 are highly expressed in colorectal cancer tissues and have a certain relationship with the occurrence and development of colorectal cancer.The expression levels of PKM2 and Notch1 are also related to the effect of chemotherapy and radiotherapy,which seriously affect the prognosis of patients with colorectal cancer, and both are the key targets of colorectal cancer treatment and research. PKM2 mainly regulates the metabolism and gene transcription of can-cer cells, and promotes the development of tumor under the regulation of some lncRNAs. It can also be used as an auxiliary diagnostic index of colorectal cancer. The Notch1 can play the similar role as PKM2 under the regulation of miRNAs and autophagy, and cause the metastasis of colorectal cancer by promoting ep-ithelial-mesenchymal transition(EMT). In addition, PKM2 and Notch1 are associated with the Wnt/β-catenin signaling pathway in colorectal cancer, but it is not clear whether there is a correlation between them. Here the research progress of PKM2 and Notch1 in colorectal cancer were discussed, which would provide a new idea for the targeted treatment of colorectal cancer.
Studies have shown that pyruvate kinase M2(PKM2) and Notch1 are highly expressed in colorectal cancer tissues and have a certain relationship with the occurrence and development of colorectal cancer.The expression levels of PKM2 and Notch1 are also related to the effect of chemotherapy and radiotherapy,which seriously affect the prognosis of patients with colorectal cancer, and both are the key targets of colorectal cancer treatment and research. PKM2 mainly regulates the metabolism and gene transcription of can-cer cells, and promotes the development of tumor under the regulation of some lncRNAs. It can also be used as an auxiliary diagnostic index of colorectal cancer. The Notch1 can play the similar role as PKM2 under the regulation of miRNAs and autophagy, and cause the metastasis of colorectal cancer by promoting ep-ithelial-mesenchymal transition(EMT). In addition, PKM2 and Notch1 are associated with the Wnt/β-catenin signaling pathway in colorectal cancer, but it is not clear whether there is a correlation between them. Here the research progress of PKM2 and Notch1 in colorectal cancer were discussed, which would provide a new idea for the targeted treatment of colorectal cancer.
引文
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[14] ABEYWARDANA T, OH M, JIANG L, et al. CARM1 suppresses serine synthesis by promoting PKM2 activity[J]. The Journal of Biological Chemistry, 2018, 293(39):15290-15303.
[15] FISCHER K, HOFFMANN P, VOELKL S, et al. Inhibitory effect of tumor cell-derived lactic acid on human T cells[J]. Blood,2007, 109(9):3812-3819.
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[18] LUO W, HU H, CHANG R, et al. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1[J].Cell, 2011, 145(5):732-744.
[19] YANG W, XIA Y, JI H, et al. Nuclear PKM2 regulates betacatenin transactivation upon EGFR activation[J]. Nature, 2011,480(7375):118-122.
[20] YANG W, ZHENG Y, XIA Y, et al. ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect[J]. Nature Cell Biology, 2012, 14(12):1295-1304.
[21] KOREN E, FUCHS Y. The bad seed:cancer stem cells in tumor development and resistance[J]. Drug Resistance Updates, 2016,28:1-12.
[22] LUO W, SEMENZA G L. Emerging roles of PKM2 in cell metabolism and cancer progression[J]. Trends in Endocrinology and Metabolism, 2012, 23(11):560-566.
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