髓母细胞瘤不同分子亚型中自噬的机制研究进展
Research Progress on Autophagy Mechanisms in Different Molecular Subtypes of Medulloblastoma
DOI: 10.12677/acm.2024.143969, PDF,   
作者: 凯赛·吐尔逊, 汪永新：新疆医科大学第一附属医院，新疆 乌鲁木齐
关键词: 髓母细胞瘤；自噬；SHH通路；Wnt通路；Medulloblastoma； Autophagy； SHH Pathway； Wnt Pathway
摘要: 自噬，作为一种生理过程，参与了肿瘤的发生发展。一方面，它能清除受损细胞器，抑制炎症，从而延缓肿瘤的发生；另一方面，它又能促进细胞的稳态，增强肿瘤的适应性，从而促进肿瘤的进展。髓母细胞瘤，作为儿童常见的恶性肿瘤之一，因其独特的解剖位置、细胞起源和临床表现，成为了导致儿童死亡的重要原因之一。目前研究发现，自噬在不同亚型的髓母细胞瘤中的作用存在差异，并影响疾病的进展。因此，本综述以髓母细胞瘤的分子亚型为出发点，深入探讨了自噬在髓母细胞瘤不同分子亚型中的作用机制，为髓母细胞瘤的治疗找到新的潜在治疗靶点，为患者探索出新的治疗方向。
Abstract: Autophagy, as a physiological process, plays a role in the initiation and progression of tumors. On one hand, it can clear damaged organelles and suppress inflammation, thereby slowing down tumor development; on the other hand, it can promote cellular homeostasis, enhancing the adaptability of tumors and facilitating their progression. Medulloblastoma, as one of the common malignant tumors in children, has become a significant contributor to childhood mortality due to its unique anatomical location, cell origin, and clinical manifestations. Current research indicates that the role of autophagy varies among different subtypes of medulloblastoma, influencing the course of the disease. Therefore, this review, starting from the molecular subtypes of medulloblastoma, delves into the mechanisms of autophagy in different molecular subtypes, aiming to identify new potential therapeutic targets for medulloblastoma treatment and explore novel therapeutic directions for patients.
文章引用：凯赛·吐尔逊, 汪永新. 髓母细胞瘤不同分子亚型中自噬的机制研究进展[J]. 临床医学进展, 2024, 14(3): 2247-2253. https://doi.org/10.12677/acm.2024.143969

参考文献

[1] Schakelaar, M.Y., Monnikhof, M., Crnko, S., et al. (2022) Cellular Immunotherapy for Medulloblastoma. Neuro-Oncology, 25, 617-627. [Google Scholar] [CrossRef] [PubMed]
[2] Louis, D.N., Perry, A., Wesseling, P., et al. (2021) The 2021 WHO Classification of Tumors of the Central Nervous System: A Summary. Neuro-Oncology, 23, 1231-1251. [Google Scholar] [CrossRef] [PubMed]
[3] Luzzi, S., Lucifero, A.G., Brambilla, I., et al. (2020) Targeting the Medulloblastoma: A Molecular-Based Approach. Acta Bio Medica: AteneiParmensis, 91, 79-100.
[4] Northcott, P.A., Shih, D.J., Peacock, J., et al. (2012) Subgroup Specific Structural Variation across 1,000 Medulloblastoma Genomes. Nature, 488, 49-56. [Google Scholar] [CrossRef] [PubMed]
[5] Taylor, M.D., Northcott, P.A., Korshunov, A., et al. (2012) Molecular Subgroups of Medulloblastoma: The Current Consensus. Acta Neuropathologica, 123, 465-472. [Google Scholar] [CrossRef] [PubMed]
[6] Kool, M., Korshunov, A., Remke, M., et al. (2012) Molecular Subgroups of Medulloblastoma: An International Meta-Analysis of Transcriptome, Genetic Aberrations, and Clinical Data of WNT, SHH, Group 3, and Group 4 Medulloblastomas. Acta Neuropathologica, 123, 473-484. [Google Scholar] [CrossRef] [PubMed]
[7] Li, J., Zhao, S., Lee, M., et al. (2020) Reliable Tumor Detection by Whole-Genome Methylation Sequencing of Cell-Free DNA in Cerebrospinal Fluid of Pediatric Medulloblastoma. Science Advances, 6, Eabb5427. [Google Scholar] [CrossRef] [PubMed]
[8] Li, W., He, P., Huang, Y., et al. (2021) Selective Autophagy of Intracellular Organelles: Recent Research Advances. Theranostics, 11, 222-256. [Google Scholar] [CrossRef] [PubMed]
[9] Xu, Y. and Wan, W. (2023) Acetylation in the Regulation of Autophagy. Autophagy, 19, 379-387. [Google Scholar] [CrossRef] [PubMed]
[10] Assaye, M.A. and Gizaw, S.T. (2022) Chaperone-Mediated Autophagy and Its Implications for Neurodegeneration and Cancer. International Journal of General Medicine, 15, 5635-5649. [Google Scholar] [CrossRef] 
[11] Qiao, L., Hu, J., Qiu, X., et al. (2023) LAMP2A, LAMP2B and LAMP2C: Similar Structures, Divergent Roles. Autophagy, 19, 2837-2852. [Google Scholar] [CrossRef] [PubMed]
[12] Liu, J., Wang, L., He, H., et al. (2023) The Complex Role of Chaperone-Mediated Autophagy in Cancer Diseases. Biomedicines, 11, Article No. 2050. [Google Scholar] [CrossRef] [PubMed]
[13] Santana-Codina, N., Mancias, J.D. and Kimmelman, A.C. (2017) The Role of Autophagy in Cancer. Annual Review of Cancer Biology, 1, 19-39. [Google Scholar] [CrossRef] [PubMed]
[14] Takamura, A., Komatsu, M., Hara, T., et al. (2011) Autophagy-Deficient Mice Develop Multiple Liver Tumors. Genes & Development, 25, 795-800. [Google Scholar] [CrossRef] [PubMed]
[15] Holdgaard, S.G., Cianfanelli, V., Pupo, E., et al. (2019) Selective Autophagy Maintains Centrosome Integrity and Accurate Mitosis by Turnover of Centriolar Satellites. Nature Communications, 10, Article No. 4176. [Google Scholar] [CrossRef] [PubMed]
[16] Schneider, J.L., Villarroya, J., Diaz-Carretero, A., et al. (2015) Loss of Hepatic Chapero3ne-Mediated Autophagy Accelerates Proteostasis Failure in Aging. Aging Cell, 14, 249-264. [Google Scholar] [CrossRef] [PubMed]
[17] Rao, S., Gharib, K. and Han, A. (2019) Cancer Immunosurveillance by T Cells. International Review of Cell and Molecular Biology, 342, 149-173. [Google Scholar] [CrossRef] [PubMed]
[18] Arensman, M.D., Yang, X.S., Zhong, W., et al. (2020) Anti-Tumor Immunity Influences Cancer Cell Reliance upon ATG7. Oncoimmunology, 9, Article ID: 1800162. [Google Scholar] [CrossRef] 
[19] Miller, D.R. and Thorburn, A. (2021) Autophagy and Organelle Homeostasis in Cancer. Developmental Cell, 56, 906-918. [Google Scholar] [CrossRef] [PubMed]
[20] Yamamoto, K., Venida, A., Yano, J., et al. (2020) Autophagy Promotes Immune Evasion of Pancreatic Cancer by Degrading MHC-I. Nature, 581, 100-105. [Google Scholar] [CrossRef] [PubMed]
[21] Towers, C.G. et al. (2019) Cancer Cells Upregulate NRF2 Signaling to Adapt to Autophagy Inhibition. Developmental Cell, 50, 690-703.E6. [Google Scholar] [CrossRef] [PubMed]
[22] Lin, A.W. and Lowe, S.W. (2001) Oncogenic Ras Activates the ARF-P53 Pathway to Suppress Epithelial Cell Transformation. Proceedings of the National Academy of Sciences, 98, 5025-5030. [Google Scholar] [CrossRef] [PubMed]
[23] Rosenfeldt, M.T., O’Prey, J., Morton, J.P., et al. (2013) P53 Status Determines the Role of Autophagy in Pancreatic Tumour Development. Nature, 504, 296-300. [Google Scholar] [CrossRef] [PubMed]
[24] Sursal, T., Ronecker, J.S., Dicpinigaitis, A.J., et al. (2022) Molecular Stratification of Medulloblastoma: Clinical Outcomes and Therapeutic Interventions. Anticancer Research, 42, 2225-2239. [Google Scholar] [CrossRef] [PubMed]
[25] Dhanyamraju, P.K., Patel, T.N. and Dovat, S. (2020) Medulloblastoma: “Onset of the Molecular Era”. Molecular Biology Reports, 47, 9931-9937. [Google Scholar] [CrossRef] [PubMed]
[26] Nàger, M., Sallán, M.C., Visa, A., et al. (2018) Inhibition of WNT-CTNNB1 Signaling Upregulates SQSTM1 and Sensitizes Glioblastoma Cells to Autophagy Blockers. Autophagy, 14, 619-636. [Google Scholar] [CrossRef] [PubMed]
[27] Zhou, C., Liang, Y., Zhou, L., et al. (2021) TSPAN1 Promotes Autophagy Flux and Mediates Cooperation between WNT-CTNNB1 Signaling and Autophagy via the MIR454-FAM83A-TSPAN1 Axis in Pancreatic Cancer. Autophagy, 17, 3175-3195. [Google Scholar] [CrossRef] [PubMed]
[28] Bharambe, H.S., Paul, R., Panwalkar, P., et al. (2019) Downregulation of MiR-204 Expression Defines a Highly Aggressive Subset of Group 3/Group 4 Medulloblastomas. Acta Neuropathologica Communications, 7, Article No. 52. [Google Scholar] [CrossRef] [PubMed]
[29] Hwang, H.J. and Kim, Y.K. (2023) The Role of LC3B in Autophagy as an RNA-Binding Protein. Autophagy, 19, 1028-1030. [Google Scholar] [CrossRef] [PubMed]
[30] Bjørkøy, G., Lamark, T., Pankiv, S., et al. (2009) Monitoring Autophagic Degradation of P62/SQSTM1. Methods in Enzymology, 452, 181-197. [Google Scholar] [CrossRef] 
[31] Yin, Y., Zhang, B., Wang, W., et al. (2014) MiR-204-5p Inhibits Proliferation and Invasion and Enhances Chemotherapeutic Sensitivity of Colorectal Cancer Cells by Downregulating RAB22A. Clinical Cancer Research, 20, 6187-6199. [Google Scholar] [CrossRef] 
[32] Zhou, L. and Ma, J. (2022) MIR99AHG/MiR-204-5p/TXNIP/Nrf2/ARE Signaling Pathway Decreases Glioblastoma Temozolomide Sensitivity. Neurotoxicity Research, 40, 1152-1162. [Google Scholar] [CrossRef] [PubMed]
[33] Garcia-Lopez, J., Kumar, R., Smith, K.S. and Northcott, P.A. (2021) Deconstructing Sonic Hedgehog Medulloblastoma: Molecular Subtypes, Drivers, and Beyond. Trends in Genetics, 37, 235-250. [Google Scholar] [CrossRef] [PubMed]
[34] Paul, R., Bharambe, H. AndShirsat, N.V. (2020) Autophagy Inhibition Impairs the Invasion Potential of Medulloblastoma Cells. Molecular Biology Reports, 47, 5673-5680. [Google Scholar] [CrossRef] [PubMed]
[35] Bhoopathi, P, Chetty, C., Gujrati, M., et al. (2010) Cathepsin B Facilitates Autophagy Mediated Apoptosis in SPARC Overexpressed Primitive Neuroectodermal Tumor Cells. Cell Death & Differentiation, 17, 1529-1539. [Google Scholar] [CrossRef] [PubMed]
[36] Dudley, L.J., Cabodevilla, A.G., Makar, A.N., et al. (2019) Intrinsic Lipid Binding Activity of ATG16L1 Supports Efficient Membrane Anchoring and Autophagy. The EMBO Journal, 38, E100554. [Google Scholar] [CrossRef] [PubMed]
[37] Bouras, E., Karakioulaki, M., Bougioukas, K.I., et al. (2019) Gene Promoter Methylation and Cancer: An Umbrella Review. Gene, 710, 333-340. [Google Scholar] [CrossRef] [PubMed]
[38] Milla, L.A., González-Ramírez, C.N. and Palma, V. (2012) Sonic Hedgehog in Cancer Stem Cells: A Novel Link with Autophagy. Biological Research, 45, 223-230. [Google Scholar] [CrossRef] 
[39] Menyhárt, O. and Győrffy, B. (2019) Principles of Tumorigenesis and Emerging Molecular Drivers of SHH-Activated Medulloblastomas. Annals of Clinical and Translational Neurology, 6, 990-1005. [Google Scholar] [CrossRef] [PubMed]
[40] Samkari, A., White, J. and Packer, R. (2015) SHH Inhibitors for the Treatment of Medulloblastoma. Annals of Clinical and Translational Neurology, 15, 763-770. [Google Scholar] [CrossRef] [PubMed]
[41] Lhermitte, B. Blandin, A.F., Coca, A., et al. (2021) Signaling Pathway Deregulation and Molecular Alterations across Pediatric Medulloblastomas. Neurochirurgie, 67, 39-45. [Google Scholar] [CrossRef] [PubMed]
[42] Li, X., Lyu, Y., Li, J. and Wang, X. (2022) AMBRA1 and Its Role as a Target for Anticancer Therapy. Frontiers in Oncology, 12, Article ID: 946086. [Google Scholar] [CrossRef] [PubMed]
[43] Nazio, F., Po, A., Abballe, L., et al. (2021) Targeting Cancer Stem Cells in Medulloblastoma by Inhibiting AMBRA1 Dual Function in Autophagy and STAT3 Signalling. Acta Neuropathologica, 142, 537-564. [Google Scholar] [CrossRef] [PubMed]
[44] Zou, H., Poore, B., Broniscer, A., Pollack, I.F. and Hu, B. (2020) Molecular Heterogeneity and Cellular Diversity: Implications for Precision Treatment in Medulloblastoma. Cancers, 12, Article No. 643. [Google Scholar] [CrossRef] [PubMed]
[45] Singh, V.S., Dakhole, N.A., Deogharkar, A., et al. (2017) Restoration of MiR-30a Expression Inhibits Growth, Tumorigenicity of Medulloblastoma Cells Accompanied by Autophagy Inhibition. Biochemical and Biophysical Research Communications, 491, 946-952. [Google Scholar] [CrossRef] [PubMed]
[46] Buzzetti, M., Morlando, S., Solomos, D., et al. (2021) Pre-Therapeutic Efficacy of the CDK Inhibitor Dinaciclib in Medulloblastoma Cells. Scientific Reports, 11, Article No. 5374. [Google Scholar] [CrossRef] [PubMed]

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