PKM2在消化系统疾病中的研究进展
Research Progress of PKM2 in Digestive System Diseases
DOI: 10.12677/acm.2025.1561883, PDF,    科研立项经费支持
作者: 杨少雷, 梁丹丹:济宁医学院临床医学院(附属医院),山东 济宁;周广玺, 朱凤琴*:济宁医学院附属医院消化内科,山东 济宁
关键词: M2型丙酮酸激酶消化系统炎症性肠病肿瘤Pyruvate Kinase M2 Digestive System Inflammatory Bowel Disease Tumor
摘要: M2型丙酮酸激酶(Pyruvate Kinase M2, PKM2)是丙酮酸激酶家族中的一种重要成员,广泛存在于多种细胞类型中。近年来的研究表明,PKM2不仅在糖酵解过程中发挥关键作用,还具有调节细胞代谢、增殖、凋亡及免疫反应等多重功能。在消化系统疾病的发生和发展中,PKM2的作用日益受到关注。本文重点总结了PKM2在消化系统恶性肿瘤和炎症性肠病中的研究进展,探讨其在疾病发生中的分子机制,分析其在消化系统疾病中的潜在治疗价值,尤其是PKM2作为靶向治疗策略的可能性。
Abstract: M2 pyruvate kinase (Pyruvate Kinase M2, PKM2) is an important member of the pyruvate kinase family, which is widely present in many cell types. Recent studies have shown that PKM2 not only plays a key role in glycolysis, but also has multiple functions in regulating cell metabolism, proliferation, apoptosis and immune response. Especially in the occurrence and development of digestive system diseases, the role of PKM2 has received increasing attention. In this paper, we focus on summarizing the research progress of PKM2 in digestive malignant tumors and inflammatory bowel disease, exploring its molecular mechanism in disease development, and analyzing its potential therapeutic value in digestive diseases, especially the possibility of PKM2 as a targeted therapeutic strategy.
文章引用:杨少雷, 梁丹丹, 周广玺, 朱凤琴. PKM2在消化系统疾病中的研究进展[J]. 临床医学进展, 2025, 15(6): 1529-1536. https://doi.org/10.12677/acm.2025.1561883

参考文献

[1] Dey, P., Kundu, A., Sachan, R., Park, J.H., Ahn, M.Y. and Yoon, K. (2019) PKM2 Knockdown Induces Autophagic Cell Death via AKT/mTOR Pathway in Human Prostate Cancer Cells. Cell Physiol Biochem, 52, 1535-1552.
[2] Yang, W. and Lu, Z. (2015) Pyruvate Kinase M2 at a Glance. Journal of Cell Science, 128, 1655-1660. [Google Scholar] [CrossRef] [PubMed]
[3] Zhang, Z., Deng, X., Liu, Y., Liu, Y., Sun, L. and Chen, F. (2019) PKM2, Function and Expression and Regulation. Cell & Bioscience, 9, Article No. 52. [Google Scholar] [CrossRef] [PubMed]
[4] Viola, A., Munari, F., Sánchez-Rodríguez, R., Scolaro, T. and Castegna, A. (2019) The Metabolic Signature of Macrophage Responses. Frontiers in Immunology, 10, Article 1462. [Google Scholar] [CrossRef] [PubMed]
[5] Chen, T., Wang, H., Liu, J., Cheng, H., Hsu, S., Wu, M., et al. (2019) Mutations in the PKM2 Exon-10 Region Are Associated with Reduced Allostery and Increased Nuclear Translocation. Communications Biology, 2, Article No. 105. [Google Scholar] [CrossRef] [PubMed]
[6] Shirai, T., Nazarewicz, R.R., Wallis, B.B., Yanes, R.E., Watanabe, R., Hilhorst, M., et al. (2016) The Glycolytic Enzyme PKM2 Bridges Metabolic and Inflammatory Dysfunction in Coronary Artery Disease. Journal of Experimental Medicine, 213, 337-354. [Google Scholar] [CrossRef] [PubMed]
[7] Zahra, K., Dey, T., Ashish, Mishra, S.P. and Pandey, U. (2020) Pyruvate Kinase M2 and Cancer: The Role of PKM2 in Promoting Tumorigenesis. Frontiers in Oncology, 10, Article 159. [Google Scholar] [CrossRef] [PubMed]
[8] Zhang, Y. (2014) Inflammatory Bowel Disease: Pathogenesis. World Journal of Gastroenterology, 20, 91-99. [Google Scholar] [CrossRef] [PubMed]
[9] An, J., Liu, Y., Wang, Y., Fan, R., Hu, X., Zhang, F., et al. (2022) The Role of Intestinal Mucosal Barrier in Autoimmune Disease: A Potential Target. Frontiers in Immunology, 13, Article 871713. [Google Scholar] [CrossRef] [PubMed]
[10] Yao, Y., Shang, W., Bao, L., Peng, Z. and Wu, C. (2024) Epithelial‐Immune Cell Crosstalk for Intestinal Barrier Homeostasis. European Journal of Immunology, 54, e2350631. [Google Scholar] [CrossRef] [PubMed]
[11] Palsson-McDermott, E.M., Curtis, A.M., Goel, G., Lauterbach, M.A.R., Sheedy, F.J., Gleeson, L.E., et al. (2015) Pyruvate Kinase M2 Regulates HIF-1α Activity and Il-1β Induction and Is a Critical Determinant of the Warburg Effect in LPS-Activated Macrophages. Cell Metabolism, 21, 65-80. [Google Scholar] [CrossRef] [PubMed]
[12] Yunna, C., Mengru, H., Lei, W. and Weidong, C. (2020) Macrophage M1/M2 polarization. European Journal of Pharmacology, 877, Article ID: 173090. [Google Scholar] [CrossRef] [PubMed]
[13] 张迪, 王丽娟, 李冲, 等. PKM2缺失通过巨噬细胞极化促进溃疡性结肠炎黏膜修复[J]. 中国病理生理杂志, 2024, 40(7): 1163-1172.
[14] Chung-Faye, G., Hayee, B., Maestranzi, S., Donaldson, N., Forgacs, I. and Sherwood, R. (2007) Fecal M2-Pyruvate Kinase (M2-PK): A Novel Marker of Intestinal Inflammation. Inflammatory Bowel Diseases, 13, 1374-1378. [Google Scholar] [CrossRef] [PubMed]
[15] Tang, Q., Ji, Q., Xia, W., Li, L., Bai, J., Ni, R., et al. (2014) Pyruvate Kinase M2 Regulates Apoptosis of Intestinal Epithelial Cells in Crohn’s Disease. Digestive Diseases and Sciences, 60, 393-404. [Google Scholar] [CrossRef] [PubMed]
[16] Gao, J., Zhao, Y., Li, T., Gan, X. and Yu, H. (2022) The Role of PKM2 in the Regulation of Mitochondrial Function: Focus on Mitochondrial Metabolism, Oxidative Stress, Dynamic, and Apoptosis. PKM2 in Mitochondrial Function. Oxidative Medicine and Cellular Longevity, 2022, Article ID: 7702681. [Google Scholar] [CrossRef] [PubMed]
[17] Canal, F. and Perret, C. (2012) PKM2: A New Player in the β-Catenin Game. Future Oncology, 8, 395-398. [Google Scholar] [CrossRef] [PubMed]
[18] Warburg, O. (1956) On the Origin of Cancer Cells. Science, 123, 309-314. [Google Scholar] [CrossRef] [PubMed]
[19] Wong, N., De Melo, J. and Tang, D. (2013) PKM2, a Central Point of Regulation in Cancer Metabolism. International Journal of Cell Biology, 2013, Article ID: 242513. [Google Scholar] [CrossRef] [PubMed]
[20] Prakasam, G., Iqbal, M.A., Bamezai, R.N.K. and Mazurek, S. (2018) Posttranslational Modifications of Pyruvate Kinase M2: Tweaks That Benefit Cancer. Frontiers in Oncology, 8, Article 22. [Google Scholar] [CrossRef] [PubMed]
[21] Yin, L., Shi, J., Zhang, J., Lin, X., Jiang, W., Zhu, Y., et al. (2023) PKM2 Is a Potential Prognostic Biomarker and Related to Immune Infiltration in Lung Cancer. Scientific Reports, 13, Article No. 22243. [Google Scholar] [CrossRef] [PubMed]
[22] Ishfaq, M., Bashir, N., Riaz, S.K., Manzoor, S., Khan, J.S., Bibi, Y., et al. (2022) Expression of HK2, PKM2, and PFKM Is Associated with Metastasis and Late Disease Onset in Breast Cancer Patients. Genes, 13, Article 549. [Google Scholar] [CrossRef] [PubMed]
[23] Lee, Y., Min, J.K., Kim, J., Cap, K.C., Islam, R., Hossain, A.J., et al. (2021) Multiple Functions of Pyruvate Kinase M2 in Various Cell Types. Journal of Cellular Physiology, 237, 128-148. [Google Scholar] [CrossRef] [PubMed]
[24] Xiaoyu, H., Yiru, Y., Shuisheng, S., Keyan, C., Zixing, Y., Shanglin, C., et al. (2018) The mTOR Pathway Regulates PKM2 to Affect Glycolysis in Esophageal Squamous Cell Carcinoma. Technology in Cancer Research & Treatment, 17. [Google Scholar] [CrossRef] [PubMed]
[25] Ma, R., Liu, Q., Zheng, S., Liu, T., Tan, D. and Lu, X. (2019) PKM2‐Regulated STAT3 Promotes Esophageal Squamous Cell Carcinoma Progression via TGF‐β1‐Induced EMT. Journal of Cellular Biochemistry, 120, 11539-11550. [Google Scholar] [CrossRef] [PubMed]
[26] Fukuda, S., Miyata, H., Miyazaki, Y., Makino, T., Takahashi, T., Kurokawa, Y., et al. (2015) Pyruvate Kinase M2 Modulates Esophageal Squamous Cell Carcinoma Chemotherapy Response by Regulating the Pentose Phosphate Pathway. Annals of Surgical Oncology, 22, 1461-1468. [Google Scholar] [CrossRef] [PubMed]
[27] Lu, J., Chen, M., Gao, S., Yuan, J., Zhu, Z. and Zou, X. (2018) LY294002 Inhibits the Warburg Effect in Gastric Cancer Cells by Downregulating Pyruvate Kinase M2. Oncology Letters, 15, 4358-4364. [Google Scholar] [CrossRef] [PubMed]
[28] Shiroki, T., Yokoyama, M., Tanuma, N., Maejima, R., Tamai, K., Yamaguchi, K., et al. (2017) Enhanced Expression of the M2 Isoform of Pyruvate Kinase Is Involved in Gastric Cancer Development by Regulating Cancer‐Specific Metabolism. Cancer Science, 108, 931-940. [Google Scholar] [CrossRef] [PubMed]
[29] Gao, W., Wang, J., Xu, Y., Yu, H., Yi, S., Bai, C., et al. (2024) Research Progress in the Metabolic Reprogramming of Hepatocellular Carcinoma (Review). Molecular Medicine Reports, 30, Article No. 131. [Google Scholar] [CrossRef] [PubMed]
[30] Zuo, W., Pang, Q., Zhu, X., Yang, Q., Zhao, Q., He, G., et al. (2024) Heat Shock Proteins as Hallmarks of Cancer: Insights from Molecular Mechanisms to Therapeutic Strategies. Journal of Hematology & Oncology, 17, Article No. 81. [Google Scholar] [CrossRef] [PubMed]
[31] Li, S., Hao, L., Li, N., Hu, X., Yan, H., Dai, E., et al. (2024) Targeting the Hippo/YAP1 Signaling Pathway in Hepatocellular Carcinoma: From Mechanisms to Therapeutic Drugs (Review). International Journal of Oncology, 65, Article No. 88. [Google Scholar] [CrossRef] [PubMed]
[32] Taniguchi, K., Sugito, N., Shinohara, H., Kuranaga, Y., Inomata, Y., Komura, K., et al. (2018) Organ-Specific MicroRNAs (MIR122, 137, and 206) Contribute to Tissue Characteristics and Carcinogenesis by Regulating Pyruvate Kinase M1/2 (PKM) Expression. International Journal of Molecular Sciences, 19, Article 1276. [Google Scholar] [CrossRef] [PubMed]
[33] Al-Rugeebah, A., Alanazi, M. and Parine, N.R. (2019) MEG3: An Oncogenic Long Non-Coding RNA in Different Cancers. Pathology & Oncology Research, 25, 859-874. [Google Scholar] [CrossRef] [PubMed]
[34] Bian, Z., Zhang, J., Li, M., Feng, Y., Wang, X., Zhang, J., et al. (2018) LncRNA-Fezf1-as1 Promotes Tumor Proliferation and Metastasis in Colorectal Cancer by Regulating PKM2 Signaling. Clinical Cancer Research, 24, 4808-4819. [Google Scholar] [CrossRef] [PubMed]
[35] Zhang, Y., Wang, M., Meng, F., Yang, M., Chen, Y., Guo, X., et al. (2022) A Novel SRSF3 Inhibitor, SFI003, Exerts Anticancer Activity against Colorectal Cancer by Modulating the SRSF3/DHCR24/ROS Axis. Cell Death Discovery, 8, Article No. 238. [Google Scholar] [CrossRef] [PubMed]
[36] Liang, F., Li, Q., Li, X., Li, Z., Gong, Z., Deng, H., et al. (2016) TSC22D2 Interacts with PKM2 and Inhibits Cell Growth in Colorectal Cancer. International Journal of Oncology, 49, 1046-1056. [Google Scholar] [CrossRef] [PubMed]
[37] Zhou, H., Liu, Z., Wang, Y., Wen, X., Amador, E.H., Yuan, L., et al. (2022) Colorectal Liver Metastasis: Molecular Mechanism and Interventional Therapy. Signal Transduction and Targeted Therapy, 7, Article No. 70. [Google Scholar] [CrossRef] [PubMed]
[38] Demaria, M. and Poli, V. (2012) PKM2, STAT3 and HIF-1α. JAK-STAT, 1, 194-196. [Google Scholar] [CrossRef] [PubMed]
[39] Li, M., Li, F., Zhu, C., Zhang, C., Le, Y., Li, Z., et al. (2025) The Glycolytic Enzyme PKM2 Regulates Inflammatory Osteoclastogenesis by Modulating STAT3 Phosphorylation. Journal of Biological Chemistry, 301, Article ID: 108389. [Google Scholar] [CrossRef] [PubMed]
[40] 李菲菲, 张祉薇, 于宏杰, 等. STAT3在结直肠癌发生发展中的作用机制[J]. 中国细胞生物学学报, 2021, 43(1): 93-102.
[41] Azoitei, N., Becher, A., Steinestel, K., Rouhi, A., Diepold, K., Genze, F., et al. (2016) PKM2 Promotes Tumor Angiogenesis by Regulating HIF-1α through NF-κB Activation. Molecular Cancer, 15, Article No. 3. [Google Scholar] [CrossRef] [PubMed]
[42] Wang, J., Zhu, W., Han, J., Yang, X., Zhou, R., Lu, H., et al. (2021) The Role of the HIF‐1α/ALYREF/PKM2 Axis in Glycolysis and Tumorigenesis of Bladder Cancer. Cancer Communications, 41, 560-575. [Google Scholar] [CrossRef] [PubMed]
[43] He, C., Bian, Y., Xue, Y., Liu, Z., Zhou, K., Yao, C., et al. (2016) Pyruvate Kinase M2 Activates mTORC1 by Phosphorylating AKT1S1. Scientific Reports, 6, Article No. 21524. [Google Scholar] [CrossRef] [PubMed]
[44] Bye, W.A., Nguyen, T.M., Parker, C.E., Jairath, V. and East, J.E. (2017) Strategies for Detecting Colon Cancer in Patients with Inflammatory Bowel Disease. Cochrane Database of Systematic Reviews, 9, CD000279. [Google Scholar] [CrossRef] [PubMed]
[45] Zhang, Q., Liu, Q., Zheng, S., Liu, T., Yang, L., Han, X., et al. (2021) Shikonin Inhibits Tumor Growth of ESCC by Suppressing PKM2 Mediated Aerobic Glycolysis and STAT3 Phosphorylation. Journal of Cancer, 12, 4830-4840. [Google Scholar] [CrossRef] [PubMed]
[46] Sun, Q., Gong, T., Liu, M., Ren, S., Yang, H., Zeng, S., et al. (2022) Shikonin, a Naphthalene Ingredient: Therapeutic Actions, Pharmacokinetics, Toxicology, Clinical Trials and Pharmaceutical Researches. Phytomedicine, 94, Article ID: 153805. [Google Scholar] [CrossRef] [PubMed]
[47] Anastasiou, D., Yu, Y., Israelsen, W.J., Jiang, J., Boxer, M.B., Hong, B.S., et al. (2012) Pyruvate Kinase M2 Activators Promote Tetramer Formation and Suppress Tumorigenesis. Nature Chemical Biology, 8, 839-847. [Google Scholar] [CrossRef] [PubMed]