抑癌基因SPOP在前列腺癌中的研究进展
Tumor Suppressor Gene SPOP in Prostate Cancer: A Review of Research Progress
摘要: 前列腺癌(prostate cancer, PCa)仍是全球男性第二大常见癌症，发病率逐年上升，严重威胁男性健康。随着基因组学及蛋白组学的发展，我们对前列腺的基因组及分子复杂性有了新的认识。斑点型锌指结构蛋白(speckle-type POZ (pox virus and zinc finger) protein, SPOP)作为一个抑癌基因，当其突变或下调时，可促进肿瘤发生，本文就SPOP在PCa中发挥的重要作用及其最新的研究进展作一个系统的综述。
Abstract: Prostate cancer is still the second most common cancer in men in the world, and its incidence is increasing year by year, seriously threatening men’s health. With the development of genomics and proteomics, we have a new understanding of the genome and molecular complexity of the prostate. SPOP, as a tumor suppressor gene, can promote tumorigenesis when it is mutated or down-regulated. This article provides a systematic review of SPOP’s important role in prostate cancer and its latest research progress.
文章引用：马俊豪, 李亚东, 谭伟, 刘川. 抑癌基因SPOP在前列腺癌中的研究进展[J]. 临床医学进展, 2022, 12(4): 2857-2863. https://doi.org/10.12677/ACM.2022.124410

参考文献

[1] Bray, F., et al. (2018) Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68, 394-424. [Google Scholar] [CrossRef] [PubMed]
[2] Shoag, J., et al. (2016) Clinical Variability and Molecular Heterogeneity in Prostate Cancer. Asian Journal of Andrology, 18, 543-548. [Google Scholar] [CrossRef] 
[3] Beroukhim, R., Mermel, C.H., Porter, D., et al. (2010) The Landscape of Somatic Copy-Number Alteration across Human Cancers. Nature, 463, 899-905.
[4] Barbieri, C.E., et al. (2012) Exome Sequencing Identifies Recurrent SPOP, FOXA1 and MED12 Mutations in Prostate Cancer. Nature Genetics, 44, 685-689. [Google Scholar] [CrossRef] [PubMed]
[5] Petroski, M.D. and Deshaies, R.J. (2005) Function and Regulation of cullin-RING Ubiquitin Ligases. Nature Reviews Molecular Cell Biology, 6, 9-20. [Google Scholar] [CrossRef] [PubMed]
[6] Wang, Z., Liu, P., Inuzuka, H., et al. (2014) Roles of F-Box Proteins in Cancer. Nature Reviews Cancer, 14, 233-247. [Google Scholar] [CrossRef] [PubMed]
[7] Errington, W.J., Khan, M.Q., Bueler, S.A., et al. (2012) Adaptor Protein Self-Assembly Drives the Control of a Cullin-RING Ubiquitin Ligase. Structure, 20, 1141-1153. [Google Scholar] [CrossRef] [PubMed]
[8] Zhuang, M., Calabrese, M.F., Liu, J., et al. (2009) Structures of SPOP-Substrate Complexes: Insights into Molecular Architectures of BTB-Cul3 Ubiquitin Ligases. Molecular Cell, 36, 39-50. [Google Scholar] [CrossRef] [PubMed]
[9] Stogios, P.J., Downs, G.S., Jauhal, J.J., et al. (2005) Sequence and Structural Analysis of BTB Domain Proteins. Genome Biology, 6, R82. [Google Scholar] [CrossRef] [PubMed]
[10] El-Gebali, S., Mistry, J., Bateman, A., et al. (2019) The Pfam Protein Families Database in 2019. Nucleic Acids Research, 47, D427-D432. [Google Scholar] [CrossRef] [PubMed]
[11] Choo, K.B., Chuang, T.J., Lin, W.Y., et al. (2010) Evolutionary Expansion of SPOP and Associated TD/POZ Gene Family: Impact of Evolutionary Route on Gene Expression Pattern. Gene, 460, 39-47. [Google Scholar] [CrossRef] [PubMed]
[12] Kim, M.S., Je, E.M., Oh, J.E., et al. (2013) Mutational and Ex-pressional Analyses of SPOP, a Candidate Tumor Suppressor Gene, in Prostate, Gastric and Colorectal Cancers. APMIS, 121, 626-633. [Google Scholar] [CrossRef] [PubMed]
[13] Berger, M.F., Lawrence, M.S., Demichelis, F., et al. (2011) The Genomic Complexity of Primary Human Prostate Cancer. Nature, 470, 214-220. [Google Scholar] [CrossRef] [PubMed]
[14] Beltran, H., Wyatt, A.W., Chedgy, E.C., et al. (2017) Impact of Therapy on Genomics and Transcriptomics in High-Risk Prostate Cancer Treated with Neoadjuvant Docetaxel and Androgen Deprivation Therapy. Clinical Cancer Research, 23, 6802-6811. [Google Scholar] [CrossRef] 
[15] Boysen, G., Rodrigues, D.N., Rescigno, P., et al. (2018) SPOP-Mutated/CHD1-Deleted Lethal Prostate Cancer and Abiraterone Sensitivity. Clinical Cancer Research, 24, 5585-5593. [Google Scholar] [CrossRef] 
[16] Blattner, M., Lee, D.J., O’Reilly, C., et al. (2014) SPOP Mutations in Prostate Cancer across Demographically Diverse Patient Cohorts. Neoplasia, 16, 14-20. [Google Scholar] [CrossRef] [PubMed]
[17] Böttcher, R., Kweldam, C.F., Livingstone, J., et al. (2018) Cribriform and Intraductal Prostate Cancer Are Associated with Increased Genomic Instability and Distinct Genomic Alterations. BMC Cancer, 18, Article No. 8. [Google Scholar] [CrossRef] [PubMed]
[18] Manson-Bahr, D., Ball, R., Gundem, G., et al. (2015) Mutation Detection in Formalin-Fixed Prostate Cancer Biopsies Taken at the Time of Diagnosis Using Next-Generation DNA Sequencing. Journal of Clinical Pathology, 68, 212-217. [Google Scholar] [CrossRef] [PubMed]
[19] Zuhlke, K.A., Johnson, A.M., Tomlins, S.A., et al. (2014) Identification of a Novel Germline SPOP Mutation in a Family with Hereditary Prostate Cancer. Prostate, 74, 983-990. [Google Scholar] [CrossRef] [PubMed]
[20] Buckles, E., Qian, C., Tadros, A., et al. (2014) Identification of Speck-le-Type POZ Protein Somatic Mutations in African American Prostate Cancer. Asian Journal of Andrology, 16, 829-832. [Google Scholar] [CrossRef] 
[21] Vinceneux, A., Bruyère, F., Haillot, O., et al. (2017) Ductal Adenocarcinoma of the Prostate: Clinical and Biological Profiles. Profile, 77, 1242-1250. [Google Scholar] [CrossRef] [PubMed]
[22] Abeshouse, A., et al. (2015) The Molecular Taxonomy of Primary Prostate Cancer. Cell, 163, 1011-1025.
[23] Li, C., Ao, J., Fu, J., et al. (2011) Tumor-Suppressor Role for the SPOP Ubiquitin Ligase in Signal-Dependent Proteolysis of the Oncogenic Co-Activator SRC-3/AIB1. Oncogene, 30, 4350-4364. [Google Scholar] [CrossRef] [PubMed]
[24] An, J., Wang, C., Deng, Y., et al. (2014) Destruction of Full-Length Androgen Receptor by Wild-Type SPOP, But Not Prostate-Cancer-Associated Mutants. Cell Reports, 6, 657-669. [Google Scholar] [CrossRef] [PubMed]
[25] Geng, C., Rajapakshe, K., Shah, S.S., et al. (2014) Androgen Receptor Is the Key Transcriptional Mediator of the Tumor Suppressor SPOP in Prostate Cancer. Cancer Research, 74, 5631-5643. [Google Scholar] [CrossRef] 
[26] An, J., Ren, S., Murphy, S.J., et al. (2015) Truncated ERG Oncoproteins from TMPRSS2-ERG Fusions Are Resistant to SPOP-Mediated Proteasome Degradation. Molecular Cell, 59, 904-916. [Google Scholar] [CrossRef] [PubMed]
[27] Zhang, J., Bu, X., Wang, H., et al. (2018) Cyclin D-CDK4 Ki-nase Destabilizes PD-L1 via Cullin 3-SPOP to Control Cancer Immune Surveillance. Nature, 553, 91-95. [Google Scholar] [CrossRef] [PubMed]
[28] Dai, X., Gan, W., Li, X., et al. (2017) Prostate Cancer-Associated SPOP Mutations Confer Resistance to BET Inhibitors through Stabilization of BRD4. Nature Medicine, 23, 1063-1071. [Google Scholar] [CrossRef] [PubMed]
[29] Boysen, G., Barbieri, C.E., Prandi, D., et al. (2015) SPOP Mutation Leads to Genomic Instability in Prostate Cancer. Elife, 4, e09207. [Google Scholar] [CrossRef] 
[30] Copeland, B.T., Du, J., Pal, S.K., et al. (2019) Factors That Influence the Androgen Receptor Cistrome in Benign and Malignant Prostate Cells. Molecular Oncology, 13, 2616-2632. [Google Scholar] [CrossRef] [PubMed]
[31] Tomlins, S.A., Rhodes, D.R., Perner, S., et al. (2005) Recurrent Fusion of TMPRSS2 and ETS Transcription Factor Genes in Prostate Cancer. Science, 310, 644-648. [Google Scholar] [CrossRef] [PubMed]
[32] Nam, R.K., Sugar, L., Yang, W., et al. (2007) Expression of the TMPRSS2:ERG Fusion Gene Predicts Cancer Recurrence after Surgery for Localised Prostate Cancer. British Journal of Cancer, 97, 1690-1695. [Google Scholar] [CrossRef] [PubMed]
[33] Shoag, J. and Barbieri, C.E. (2016) Clinical Variability and Molecular Heterogeneity in Prostate Cancer. Asian Journal of Andrology, 18, 543-548. [Google Scholar] [CrossRef] 
[34] Gan, W., Dai, X., Lunardi, A., et al. (2015) SPOP Promotes Ubiquitination and Degradation of the ERG Oncoprotein to Suppress Prostate Cancer Progression. Molecular Cell, 59, 917-930. [Google Scholar] [CrossRef] [PubMed]
[35] Blattner, M., Liu, D., Robinson, B.D., et al. (2017) SPOP Mutation Drives Prostate Tumorigenesis in Vivo through Coordinate Regulation of PI3K/mTOR and AR Signaling. Cancer Cell, 31, 436-451. [Google Scholar] [CrossRef] [PubMed]
[36] Shoag, J., Liu, D., Blattner, M., et al. (2018) SPOP Mutation Drives Prostate Neoplasia without Stabilizing Oncogenic Transcription Factor ERG. Journal of Clinical Investigation, 128, 381-386. [Google Scholar] [CrossRef] 
[37] Jeggo, P.A., Pearl, L.H. and Carr, A.M. (2016) DNA Repair, Genome Stability and Cancer: A Historical Perspective. Nature Reviews Cancer, 16, 35-42. [Google Scholar] [CrossRef] [PubMed]
[38] Hjorth-Jensen, K., Maya-Mendoza, A., Dalgaard, N., et al. (2018) SPOP Promotes Transcriptional Expression of DNA Repair and Replication Factors to Prevent Replication Stress and Genomic Instability. Nucleic Acids Research, 46, 9484-9495. [Google Scholar] [CrossRef] [PubMed]
[39] Zhang, D., Wang, H., Sun, M., et al. (2014) Speckle-Type POZ Protein, SPOP, Is Involved in the DNA Damage Response. Carcinogenesis, 35, 1691-1697. [Google Scholar] [CrossRef] [PubMed]
[40] El Bezawy, R., Tripari, M., Percio, S., et al. (2020) SPOP Deregulation Improves the Radiation Response of Prostate Cancer Models by Impairing DNA Damage Repair. Cancers, 12, 1462. [Google Scholar] [CrossRef] [PubMed]
[41] Siu, M.K., Wong, E.S., Kong, D.S., et al. (2013) Stem Cell Transcription Factor NANOG Controls Cell Migration and Invasion via Dysregulation of E-Cadherin and FoxJ1 and Contributes to Adverse Clinical Outcome in Ovarian Cancers. Oncogene, 32, 3500-3509. [Google Scholar] [CrossRef] [PubMed]
[42] Wong, O.G. and Cheung, A.N. (2016) Stem Cell Transcription Factor NANOG in Cancers—Is Eternal Youth a Curse? Expert Opinion on Therapeutic Targets, 20, 407-417. [Google Scholar] [CrossRef] [PubMed]
[43] Zhang, J., Chen, M., Zhu, Y., et al. (2019) SPOP Promotes Nanog Destruction to Suppress Stem Cell Traits and Prostate Cancer Progression. Developmental Cell, 48, 329-344.e325. [Google Scholar] [CrossRef] [PubMed]
[44] Huang, X., Wullschleger, S., Shpiro, N., et al. (2008) Important Role of the LKB1-AMPK Pathway in Suppressing Tumorigenesis in PTEN-Deficient Mice. Biochemical Journal, 412, 211-221. [Google Scholar] [CrossRef] 
[45] Zadra, G., Photopoulos, C., Tyekucheva, S., et al. (2014) A Novel Direct Activator of AMPK Inhibits Prostate Cancer Growth by Blocking Lipogenesis. EMBO Molecular Medicine, 6, 519-538. [Google Scholar] [CrossRef] [PubMed]
[46] Hirsch, H.A., Iliopoulos, D., Tsichlis, P.N., et al. (2009) Metformin Selectively Targets Cancer Stem Cells, and Acts Together with Chemotherapy to Block Tumor Growth and Prolong Remission. Cancer Research, 69, 7507-7511. [Google Scholar] [CrossRef] 
[47] Wang, X., Jin, J., Wan, F., et al. (2019) AMPK Promotes SPOP-Mediated NANOG Degradation to Regulate Prostate Cancer Cell Stemness. Developmental Cell, 48, 345-360.e347. [Google Scholar] [CrossRef] [PubMed]
[48] Swami, U., Isaacsson Velho, P., Nussenzveig, R., et al. (2020) Association of SPOP Mutations with Outcomes in Men with de Novo Metastatic Castration-Sensitive Prostate Cancer. European Urology, 78, 652-656. [Google Scholar] [CrossRef] [PubMed]
[49] Zhu, Y., Wen, J., Huang, G., et al. (2021) CHD1 and SPOP Synergistically Protect Prostate Epithelial Cells from DNA Damage. Prostate, 81, 81-88. [Google Scholar] [CrossRef] [PubMed]

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