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CBX6在肿瘤侵袭与迁移中的作用机制研究进展

Abstract

CBX6（Chromobox 6）是多梳抑制复合物1（Polycomb Repressive Complex 1,PRC1）的关键组成部分，具有表观遗传调控功能，通过结合H3K27me3实现基因转录抑制。近年来，CBX6在肿瘤侵袭与迁移中的作用受到广泛关注，研究发现其可能通过调节上皮-间质转化（EMT）、调控肿瘤微环境以及介导关键信号通路影响肿瘤细胞的迁移和转移。然而，不同肿瘤类型中CBX6的作用和调控机制存在差异，甚至呈现双向调控效应。本文系统综述了CBX6在肿瘤侵袭与迁移中的研究进展，探讨其可能的分子机制，分析研究中的争议与挑战，并展望其作为潜在治疗靶点的应用前景。

Keywords

CBX6肿瘤肿瘤侵袭细胞迁移

References

  1. Senthilkumar R,Mishra R K.Novel motifs distinguish multiple homologues of Polycomb in vertebrates:expansion and diversification of the epigenetic toolkit[J].BMC Genomics,2009,10:549.
  2. Margueron R,Reinberg D.The Polycomb complex PRC2 and its mark in life[J].Nature,2011,469(7330):343-349
  3. Scelfo A,Piunti A,Pasini D.The controversial role of the Polycomb group proteins in transcription and cancer:how much do we not understand Polycomb proteins?[J].The FEBS Journal,2015,282(9):1703-1722
  4. Connelly K E,Dykhuizen E C.Compositional and functional diversity of canonical PRC1 complexes in mammals[J].Biochimica et Biophysica Acta. Gene Regulatory Mechanisms,2017,1860(2):233-245
  5. Santanach A,Blanco E,Jiang H,et al.The Polycomb group protein CBX6 is an essential regulator of embryonic stem cell identity[J].Nature Communications,2017,8(1):1235
  6. Milosevich N,Gignac M C,McFarlane J,et al.Selective Inhibition of CBX6:A Methyllysine Reader Protein in the Polycomb Family[J].ACS Medicinal Chemistry Letters,2016,7(2):139-144
  7. Morey L,Pascual G,Cozzuto L,et al.Nonoverlapping functions of the Polycomb group Cbx family of proteins in embryonic stem cells[J].Cell Stem Cell,2012,10(1):47-62
  8. Wang J,Yang B,Zhang X,et al.Chromobox proteins in cancer:Multifaceted functions and strategies for modulation(Review)[J].International Journal of Oncology,2023,62(3):36
  9. van Wijnen A J,Bagheri L,Badreldin A A,et al.Biological functions of chromobox(CBX) proteins in stem cell self-renewal,lineage-commitment,cancer and development[J].Bone,2021,143:115659
  10. Wang J,He H,Jiang Q,et al.CBX6 Promotes HCC Metastasis Via Transcription Factors Snail/Zeb1-Mediated EMT Mechanism[J].Onco Targets and Therapy,2020,13:12489-12500
  11. Deng H,Guan X,Gong L,et al.CBX6 is negatively regulated by EZH2 and plays a potential tumor suppressor role in breast cancer[J].Scientific Reports,2019,9(1):197.
  12. Li X X,Li L L,Xiong X,et al.Identification of the Prognostic Biomarkers CBX6 and CBX7 in Bladder Cancer[J].Diagnostics(Basel,Switzerland),2023,13(8):1393.
  13. Zhang Y,Weinberg R A.Epithelial-to-mesenchymal transition in cancer: complexity and opportunities[J].Frontiers of Medicine,2018,12(4):361-373
  14. Huang Y H,Hong W Q,Wei X W.The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis[J].Journal of Hematology&Oncology,2022,15(1):129
  15. Pastushenko I,Blanpain C.EMT Transition States during Tumor Progression and Metastasis[J].Trends in Cell Biology,2019,29(3):212-226
  16. Tian H,Shi H H,Yu J,et al.Biophysics Role and Biomimetic Culture Systems of ECM Stiffness in Cancer EMT[J].Global Challenges(Hoboken,NJ),2022,6(6):2100094.
  17. Xu J,Lamouille S,Derynck R.TGF-beta-induced epithelial to mesenchymal transition[J].Cell Research,2009,19(2):156-172
  18. Dofara S G,Chang S L,Diorio C.Gene Polymorphisms and Circulating Levels of MMP-2 and MMP-9:A Review of Their Role in Breast Cancer Risk[J].Anticancer Research,2020,40(7):3619-3631
  19. Gonzalez-Avila G,Sommer B,García-Hernández A A,et al.Matrix Metalloproteinases' Role in Tumor Microenvironment[J].Advances in Experimental Medicine and Biology,2020,1245:97-131
  20. Niland S,Riscanevo A X,Eble J A.Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression[J].International Journal of Molecular Sciences,2021,23(1):146
  21. Liu J Q,Xiao Q,Xiao J N,et al.Wnt/β-catenin signalling:function,biological mechanisms,and therapeutic opportunities[J].Signal Transduction and Targeted Therapy,2022,7(1):3
  22. ]Lee J H,Massagué J.TGF-β in developmental and fibrogenic EMTs[J].Seminars in Cancer Biology,2022,86(Pt 2):136-145
  23. Meurette O,Mehlen P.Notch Signaling in the Tumor Microenvironment[J].Cancer Cell,2018,34(4):536-548
  24. Wang J Q,Yang K,Yang X,et al.HHLA2 promotes hepatoma cell proliferation,migration,and invasion via SPP1/PI3K/AKT signaling pathway[J].Molecular Carcinogenesis,2024,63(7):1275-1287
  25. Lv F,Du Q,Li L,et al.Eriodictyol inhibits glioblastoma migration and invasion by reversing EMT via downregulation of the P38 MAPK/GSK-3β/ZEB1 pathway[J].European Journal of Pharmacology,2021,900:174069
  26. Arneth B.Tumor Microenvironment[J].Medicina(Kaunas,Lithuania),2019,56(1):15
  27. Zheng H,Jiang W H,TIAN T,et al.CBX6 overexpression contributes to tumor progression and is predictive of a poor prognosis in hepatocellular carcinoma[J].Oncotarget,2017,8(12):18872-18884
  28. Wang J M,He H,Jiang Q C,et al.CBX6 Promotes HCC Metastasis Via Transcription Factors Snail/Zeb1-Mediated EMT Mechanism[J].OncoTargets and Therapy,2020,13:12489-12500
  29. Deng H L,Guan X W,Gong L C,et al.CBX6 is negatively regulated by EZH2 and plays a potential tumor suppressor role in breast cancer[J].Scienfic Reports,2019,9(1):197
  30. Li X M,Gou J H,Li H J,et al.Bioinformatic analysis of the expression and prognostic value of chromobox family proteins in human breast cancer[J].Scienfic Reports,2020,10(1):17739