109
Views
4
CrossRef citations to date
0
Altmetric
Review

The Controversial Role of Polyploidy in Hepatocellular Carcinoma

ORCID Icon, , &
Pages 5335-5344 | Published online: 27 Nov 2021

References

  • Epstein CJ. Cell size, nuclear content, and the development of polyploidy in the mammalian liver. Proc Natl Acad Sci U S A. 1967;57(2):327–334. doi:10.1073/pnas.57.2.327
  • Sladky VC, Knapp K, Soratroi C, et al. E2F-family members engage the PIDDosome to limit hepatocyte ploidy in liver development and regeneration. Dev Cell. 2020;52(3):335–349.e7. doi:10.1016/j.devcel.2019.12.016
  • Matsumoto T, Wakefield L, Tarlow BD, Grompe M. In vivo lineage tracing of polyploid hepatocytes reveals extensive proliferation during liver regeneration. Cell Stem Cell. 2020;26(1):34–47.e3. doi:10.1016/j.stem.2019.11.014
  • Zhang S, Nguyen LH, Zhou K, et al. Knockdown of anillin actin binding protein blocks cytokinesis in hepatocytes and reduces liver tumor development in mice without affecting regeneration. Gastroenterology. 2018;154(5):1421–1434. doi:10.1053/j.gastro.2017.12.013
  • Wilkinson PD, Delgado ER, Alencastro F, et al. The polyploid state restricts hepatocyte proliferation and liver regeneration in mice. Hepatology. 2019;69(3):1242–1258. doi:10.1002/hep.30286
  • Øvrebø JI, Edgar BA. Polyploidy in tissue homeostasis and regeneration. Development. 2018;145(14). doi:10.1242/dev.156034
  • Duncan AW. Aneuploidy, polyploidy and ploidy reversal in the liver. Semin Cell Dev Biol. 2013;24(4):347–356. doi:10.1016/j.semcdb.2013.01.003
  • Duncan AW, Hanlon Newell AE, Smith L, et al. Frequent aneuploidy among normal human hepatocytes. Gastroenterology. 2012;142(1):25–28. doi:10.1053/j.gastro.2011.10.029
  • Si-Tayeb K, Lemaigre FP, Duncan SA. Organogenesis and development of the liver. Dev Cell. 2010;18(2):175–189. doi:10.1016/j.devcel.2010.01.011
  • Zhang S, Zhou K, Luo X, et al. The polyploid state plays a tumor-suppressive role in the liver. Dev Cell. 2018;44(4):447–459.e5. doi:10.1016/j.devcel.2018.01.010
  • Guidotti JE, Bregerie O, Robert A, Debey P, Brechot C, Desdouets C. Liver cell polyploidization: a pivotal role for binuclear hepatocytes. J Biol Chem. 2003;278(21):19095–19101. doi:10.1074/jbc.M300982200
  • Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249. doi:10.3322/caac.21660
  • Davoli T, de Lange T. The causes and consequences of polyploidy in normal development and cancer. Annu Rev Cell Dev Biol. 2011;27:585–610. doi:10.1146/annurev-cellbio-092910-154234
  • Lin H, Huang YS, Fustin JM, et al. Hyperpolyploidization of hepatocyte initiates preneoplastic lesion formation in the liver. Nat Commun. 2021;12(1):645. doi:10.1038/s41467-020-20572-8
  • Matsumoto T, Wakefield L, Peters A, Peto M, Spellman P, Grompe M. Proliferative polyploid cells give rise to tumors via ploidy reduction. Nat Commun. 2021;12(1):646. doi:10.1038/s41467-021-20916-y
  • Muller M, May S, Bird TG. Ploidy dynamics increase the risk of liver cancer initiation. Nat Commun. 2021;12(1):1896. doi:10.1038/s41467-021-21897-8
  • Donne R, Saroul-Ainama M, Cordier P, Celton-Morizur S, Desdouets C. Polyploidy in liver development, homeostasis and disease. Nat Rev Gastroenterol Hepatol. 2020;17(7):391–405. doi:10.1038/s41575-020-0284-x
  • Gentric G, Desdouets C. Polyploidization in liver tissue. Am J Pathol. 2014;184(2):322–331. doi:10.1016/j.ajpath.2013.06.035
  • Celton-Morizur S, Desdouets C. Polyploidization of liver cells. Adv Exp Med Biol. 2010;676:123–135. doi:10.1007/978-1-4419-6199-0_8
  • Faggioli F, Sacco MG, Susani L, Montagna C, Vezzoni P. Cell fusion is a physiological process in mouse liver. Hepatology. 2008;48(5):1655–1664. doi:10.1002/hep.22488
  • Zhang S, Lin YH, Tarlow B, Zhu H. The origins and functions of hepatic polyploidy. Cell Cycle. 2019;18(12):1302–1315. doi:10.1080/15384101.2019.1618123
  • Diril MK, Ratnacaram CK, Padmakumar VC, et al. Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration. Proc Natl Acad Sci U S A. 2012;109(10):3826–3831. doi:10.1073/pnas.1115201109
  • Hartwell LH, Weinert TA. Checkpoints: controls that ensure the order of cell cycle events. Science. 1989;246(4930):629–634. doi:10.1126/science.2683079
  • Kurinna S, Stratton SA, Coban Z, et al. p53 regulates a mitotic transcription program and determines ploidy in normal mouse liver. Hepatology. 2013;57(5):2004–2013. doi:10.1002/hep.26233
  • Sheahan S, Bellamy CO, Treanor L, Harrison DJ, Prost S. Additive effect of p53, p21 and Rb deletion in triple knockout primary hepatocytes. Oncogene. 2004;23(8):1489–1497. doi:10.1038/sj.onc.1207280
  • Mayhew CN, Bosco EE, Fox SR, et al. Liver-specific pRB loss results in ectopic cell cycle entry and aberrant ploidy. Cancer Res. 2005;65(11):4568–4577. doi:10.1158/0008-5472.Can-04-4221
  • Edgar BA, Zielke N, Gutierrez C. Endocycles: a recurrent evolutionary innovation for post-mitotic cell growth. Nat Rev Mol Cell Biol. 2014;15(3):197–210. doi:10.1038/nrm3756
  • Radziejwoski A, Vlieghe K, Lammens T, et al. Atypical E2F activity coordinates PHR1 photolyase gene transcription with endoreduplication onset. EMBO j. 2011;30(2):355–363. doi:10.1038/emboj.2010.313
  • Davoli T, de Lange T. Telomere-driven tetraploidization occurs in human cells undergoing crisis and promotes transformation of mouse cells. Cancer Cell. 2012;21(6):765–776. doi:10.1016/j.ccr.2012.03.044
  • D’Avino PP, Giansanti MG, Petronczki M. Cytokinesis in animal cells. Cold Spring Harb Perspect Biol. 2015;7(4):a015834. doi:10.1101/cshperspect.a015834
  • Donne R, Sangouard F, Celton-Morizur S, Desdouets C. Hepatocyte polyploidy: driver or gatekeeper of chronic liver diseases. Cancers (Basel). 2021;13(20):5151. doi:10.3390/cancers13205151
  • Margall-Ducos G, Celton-Morizur S, Couton D, Brégerie O, Desdouets C. Liver tetraploidization is controlled by a new process of incomplete cytokinesis. J Cell Sci. 2007;120(Pt 20):3633–3639. doi:10.1242/jcs.016907
  • Celton-Morizur S, Merlen G, Couton D, Desdouets C. Polyploidy and liver proliferation: central role of insulin signaling. Cell Cycle. 2010;9(3):460–466. doi:10.4161/cc.9.3.10542
  • Celton-Morizur S, Merlen G, Couton D, Margall-Ducos G, Desdouets C. The insulin/Akt pathway controls a specific cell division program that leads to generation of binucleated tetraploid liver cells in rodents. J Clin Invest. 2009;119(7):1880–1887. doi:10.1172/jci38677
  • Wang MJ, Chen F, Lau JTY, Hu YP. Hepatocyte polyploidization and its association with pathophysiological processes. Cell Death Dis. 2017;8(5):e2805. doi:10.1038/cddis.2017.167
  • Hsu SH, Delgado ER, Otero PA, et al. MicroRNA-122 regulates polyploidization in the murine liver. Hepatology. 2016;64(2):599–615. doi:10.1002/hep.28573
  • Xu H, He JH, Xu SJ, et al. A group of tissue-specific microRNAs contribute to the silencing of CUX1 in different cell lineages during development. J Cell Biochem. 2018;119(7):6238–6248. doi:10.1002/jcb.26852
  • Ghafouri-Fard S, Noroozi R, Abak A, Taheri M, Salimi A. Emerging role of lncRNAs in the regulation of Rho GTPase pathway. Biomed Pharmacother. 2021;140:111731. doi:10.1016/j.biopha.2021.111731
  • Luna JM, Barajas JM, Teng KY, et al. Argonaute CLIP defines a deregulated miR-122-bound transcriptome that correlates with patient survival in human liver cancer. Mol Cell. 2017;67(3):400–410.e7. doi:10.1016/j.molcel.2017.06.025
  • Duncan AW, Taylor MH, Hickey RD, et al. The ploidy conveyor of mature hepatocytes as a source of genetic variation. Nature. 2010;467(7316):707–710. doi:10.1038/nature09414
  • Pandit SK, Westendorp B, Nantasanti S, et al. E2F8 is essential for polyploidization in mammalian cells. Nat Cell Biol. 2012;14(11):1181–1191. doi:10.1038/ncb2585
  • Miyaoka Y, Ebato K, Kato H, Arakawa S, Shimizu S, Miyajima A. Hypertrophy and unconventional cell division of hepatocytes underlie liver regeneration. Curr Biol. 2012;22(13):1166–1175. doi:10.1016/j.cub.2012.05.016
  • Kreutz C, MacNelly S, Follo M, et al. Hepatocyte ploidy is a diversity factor for liver homeostasis. Front Physiol. 2017;8:862. doi:10.3389/fphys.2017.00862
  • Knouse KA, Lopez KE, Bachofner M, Amon A. Chromosome segregation fidelity in epithelia requires tissue architecture. Cell. 2018;175(1):200–211.e13. doi:10.1016/j.cell.2018.07.042
  • Miettinen TP, Pessa HK, Caldez MJ, et al. Identification of transcriptional and metabolic programs related to mammalian cell size. Curr Biol. 2014;24(6):598–608. doi:10.1016/j.cub.2014.01.071
  • Schoenfelder KP, Fox DT. The expanding implications of polyploidy. J Cell Biol. 2015;209(4):485–491. doi:10.1083/jcb.201502016
  • Halpern KB, Tanami S, Landen S, et al. Bursty gene expression in the intact mammalian liver. Mol Cell. 2015;58(1):147–156. doi:10.1016/j.molcel.2015.01.027
  • Lin YH, Zhang S, Zhu M, et al. Mice with increased numbers of polyploid hepatocytes maintain regenerative capacity but develop fewer hepatocellular carcinomas following chronic liver injury. Gastroenterology. 2020;158(6):1698–1712 e14. doi:10.1053/j.gastro.2020.01.026
  • Hamada S, Itoh R, Fujita S. DNA distribution pattern of the so-called severe dysplasias and small carcinomas of the colon and rectum and its possible significance in the tumor progression. Cancer. 1988;61(8):1555–1562. doi:10.1002/1097-0142(19880415)61:8<1555::aid-cncr2820610812>3.0.co;2-w
  • Sato N, Mizumoto K, Nakamura M, et al. Centrosome abnormalities in pancreatic ductal carcinoma. Clin Cancer Res. 1999;5(5):963–970.
  • Lothschütz D, Jennewein M, Pahl S, et al. Polyploidization and centrosome hyperamplification in inflammatory bronchi. Inflamm Res. 2002;51(8):416–422. doi:10.1007/pl00000323
  • Bielski CM, Zehir A, Penson AV, et al. Genome doubling shapes the evolution and prognosis of advanced cancers. Nat Genet. 2018;50(8):1189–1195. doi:10.1038/s41588-018-0165-1
  • Ganem NJ, Godinho SA, Pellman D. A mechanism linking extra centrosomes to chromosomal instability. Nature. 2009;460(7252):278–282. doi:10.1038/nature08136
  • Chen HZ, Ouseph MM, Li J, et al. Canonical and atypical E2Fs regulate the mammalian endocycle. Nat Cell Biol. 2012;14(11):1192–1202. doi:10.1038/ncb2595
  • Sladky VC, Knapp K, Szabo TG, et al. PIDDosome-induced p53-dependent ploidy restriction facilitates hepatocarcinogenesis. EMBO Rep. 2020;21(12):e50893. doi:10.15252/embr.202050893
  • Fava LL, Schuler F, Sladky V, et al. The PIDDosome activates p53 in response to supernumerary centrosomes. Genes Dev. 2017;31(1):34–45. doi:10.1101/gad.289728.116
  • Bou-Nader M, Caruso S, Donne R, et al. Polyploidy spectrum: a new marker in HCC classification. Gut. 2020;69(2):355–364. doi:10.1136/gutjnl-2018-318021
  • Gentric G, Maillet V, Paradis V, et al. Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease. J Clin Invest. 2015;125(3):981–992. doi:10.1172/JCI73957
  • Sansregret L, Vanhaesebroeck B, Swanton C. Determinants and clinical implications of chromosomal instability in cancer. Nat Rev Clin Oncol. 2018;15(3):139–150. doi:10.1038/nrclinonc.2017.198
  • Targa A, Rancati G. Cancer: a CINful evolution. Curr Opin Cell Biol. 2018;52:136–144. doi:10.1016/j.ceb.2018.03.007