Overcome Cancer Drug Resistance by Targeting Epigenetic Modifications of Centrosome

Overview

Journal Cancer Drug Resist

Date 2022 May 18

PMID 35582716

Authors

Zan-Hui Jia

Xing-Gang Wang

Hong Zhang

Affiliations

Soon will be listed here.

Abstract

The centrosome is an organelle that serves as the microtubule- and actin-organizing center of human cells. Although the centrosome is small of size, it is great important on cellular function that regulates cytoskeletal organization and governs precise spindle orientation/positioning ensuring equal distribution of cellular components in cell division. Epigenetic modifications to centrosome proteins can lead to centrosome aberrations, such as disorganized spindles and centrosome amplification causing aneuploidy and genomic instability. Epigenetic disturbances are associated not only with carcinogenesis and cancer progression, but also with drug resistance to chemotherapy. In this review, we discuss mechanisms of epigenetic alteration during the centrosome biogenesis in cancer. We provide an update on the current status of clinical trials that aim to target epigenetic modifications in centrosome aberrations and to thwart drug resistance.

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References

Liu X, Winey M . The MPS1 family of protein kinases. Annu Rev Biochem. 2012; 81:561-85. PMC: 4026297. DOI: 10.1146/annurev-biochem-061611-090435. View

Moustafa-Kamal M, Gamache I, Lu Y, Li S, Teodoro J . BimEL is phosphorylated at mitosis by Aurora A and targeted for degradation by βTrCP1. Cell Death Differ. 2013; 20(10):1393-403. PMC: 3770328. DOI: 10.1038/cdd.2013.93. View

Berman H, Zhang J, Crawford Y, Gauthier M, Fordyce C, McDermott K . Genetic and epigenetic changes in mammary epithelial cells identify a subpopulation of cells involved in early carcinogenesis. Cold Spring Harb Symp Quant Biol. 2006; 70:317-27. DOI: 10.1101/sqb.2005.70.051. View

Mardin B, Lange C, Baxter J, Hardy T, Scholz S, Fry A . Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction. Nat Cell Biol. 2010; 12(12):1166-76. PMC: 3939356. DOI: 10.1038/ncb2120. View

Lomonosova E, Chinnadurai G . BH3-only proteins in apoptosis and beyond: an overview. Oncogene. 2009; 27 Suppl 1:S2-19. PMC: 2928556. DOI: 10.1038/onc.2009.39. View

Baylin S, Jones P . A decade of exploring the cancer epigenome - biological and translational implications. Nat Rev Cancer. 2011; 11(10):726-34. PMC: 3307543. DOI: 10.1038/nrc3130. View

Yu F, Thiesen J, Stratling W . Histone deacetylase-independent transcriptional repression by methyl-CpG-binding protein 2. Nucleic Acids Res. 2000; 28(10):2201-6. PMC: 105362. DOI: 10.1093/nar/28.10.2201. View

Sampson P, Liu Y, Patel N, Feher M, Forrest B, Li S . The discovery of Polo-like kinase 4 inhibitors: design and optimization of spiro[cyclopropane-1,3'[3H]indol]-2'(1'H).ones as orally bioavailable antitumor agents. J Med Chem. 2014; 58(1):130-46. DOI: 10.1021/jm5005336. View

Foster S, Wong D, Barrett M, Galloway D . Inactivation of p16 in human mammary epithelial cells by CpG island methylation. Mol Cell Biol. 1998; 18(4):1793-801. PMC: 121409. DOI: 10.1128/MCB.18.4.1793. View

10.

Pihan G, Wallace J, Zhou Y, Doxsey S . Centrosome abnormalities and chromosome instability occur together in pre-invasive carcinomas. Cancer Res. 2003; 63(6):1398-404. View

11.

Kleylein-Sohn J, Pollinger B, Ohmer M, Hofmann F, Nigg E, Hemmings B . Acentrosomal spindle organization renders cancer cells dependent on the kinesin HSET. J Cell Sci. 2012; 125(Pt 22):5391-402. DOI: 10.1242/jcs.107474. View

12.

Malumbres M, Barbacid M . Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009; 9(3):153-66. DOI: 10.1038/nrc2602. View

13.

Nam H, Naylor R, van Deursen J . Centrosome dynamics as a source of chromosomal instability. Trends Cell Biol. 2014; 25(2):65-73. PMC: 4312731. DOI: 10.1016/j.tcb.2014.10.002. View

14.

Janssen A, Kops G, Medema R . Elevating the frequency of chromosome mis-segregation as a strategy to kill tumor cells. Proc Natl Acad Sci U S A. 2009; 106(45):19108-13. PMC: 2776415. DOI: 10.1073/pnas.0904343106. View

15.

Leach F, Tokino T, Meltzer P, Burrell M, Oliner J, Smith S . p53 Mutation and MDM2 amplification in human soft tissue sarcomas. Cancer Res. 1993; 53(10 Suppl):2231-4. View

16.

Jusino S, Fernandez-Padin F, Saavedra H . Centrosome aberrations and chromosome instability contribute to tumorigenesis and intra-tumor heterogeneity. J Cancer Metastasis Treat. 2018; 4. PMC: 6205736. DOI: 10.20517/2394-4722.2018.24. View

17.

Lacey K, Jackson P, Stearns T . Cyclin-dependent kinase control of centrosome duplication. Proc Natl Acad Sci U S A. 1999; 96(6):2817-22. PMC: 15852. DOI: 10.1073/pnas.96.6.2817. View

18.

Vijayaraghavan S, Moulder S, Keyomarsi K, Layman R . Inhibiting CDK in Cancer Therapy: Current Evidence and Future Directions. Target Oncol. 2017; 13(1):21-38. DOI: 10.1007/s11523-017-0541-2. View

19.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

20.

Lingle W, Lutz W, Ingle J, Maihle N, Salisbury J . Centrosome hypertrophy in human breast tumors: implications for genomic stability and cell polarity. Proc Natl Acad Sci U S A. 1998; 95(6):2950-5. PMC: 19675. DOI: 10.1073/pnas.95.6.2950. View