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Cited by 148Pluripotent Stem Cells ResearchCancer Cells and MetastasisDevelopmental Biology and Gene Regulation

The dualistic origin of human tumors

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Liu, Jinsong·2018·Seminars in Cancer Biology
DOI 10.1016/j.semcancer.2018.07.004PMC PMC6553492
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Abstract

Life starts with a zygote, which is formed by the fusion of a haploid sperm and egg. The formation of a blastomere by cleavage division (nuclear division without an increase in cell size) is the first step in embryogenesis, after the formation of the zygote. Blastomeres are responsible for reprogramming the parental genome as a new embryonic genome for generation of the pluripotent stem cells which then differentiate by Waddington's epigenetic landscape to create a new life. Multiple authors over the past 150 years have proposed that tumors arises from development gone awry at a point within Waddington's landscape. Recent discoveries showing that differentiated somatic cells can be reprogrammed into induced pluripotent stem cells, and that somatic cell nuclear transfer can be used to successfully clone animals, have fundamentally reshaped our understanding of tumor development and origin. Differentiated somatic cells are plastic and can be induced to dedifferentiate into pluripotent stem cells. Here, I review the evidence that suggests somatic cells may have a previously overlooked endogenous embryonic program that can be activated to dedifferentiate somatic cells into stem cells of various potencies for tumor initiation. Polyploid giant cancer cells (PGCCs) have long been observed in cancer and were thought originally to be nondividing. Contrary to this belief, recent findings show that stress-induced PGCCs divide by endoreplication, which may recapitulate the pattern of cleavage-like division in blastomeres and lead to dedifferentiation of somatic cells by a programmed process known as "the giant cell cycle", which comprise four distinct but overlapping phases: initiation, self-renewal, termination and stability. Depending on the intensity and type of stress, different levels of dedifferentiation result in the formation of tumors of different grades of malignancy. Based on these results, I propose a unified dualistic model to demonstrate the origin of human tumors. The tenet of this model includes four points, as follows. 1. Tumors originate from a stem cell at a specific developmental hierarchy, which can be achieved by dualistic origin: dedifferentiation of the zygote formed by two haploid gametes (sexual reproduction) via the blastomere during normal development, or transformation from damaged or aged mature somatic cells via a blastomere-like embryonic program (asexual reproduction). 2. Initiation of the tumor begins with a stem cell that has uncoupled the differentiation from the proliferation program which results in stem cell maturation arrest. 3. The developmental hierarchy at which stem cells arrest determines the degree of malignancy: the more primitive the level at which stem cells arrest, the greater the likelihood of the tumor being malignant. 4. Environmental factors and intrinsic genetic or epigenetic alterations represent the risk factors or stressors that facilitate stem cell arrest and somatic cell dedifferentiation. However, they, per se, are not the driving force of tumorigenesis. Thus, the birth of a tumor can be viewed as a triad that originates from a stem cell via dedifferentiation through a blastomere or blastomere-like program, which then differentiates along Waddington's landscape, and arrests at a developmental hierarchy. Blocking the PGCC-mediated dedifferentiation process and inducing their differentiation may represent a novel alternative approach to eliminate the tumor occurrence and therapeutic resistance.

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  • Epithelial cell dedifferentiation is a critical cell state transition during tumorigenesis and confers tumor cells high proliferation capacity and progenitor-like fate through multidimensional reprogramming.

    “Epithelial cell dedifferentiation is recognized as a critical cell state transition during tumorigenesis and confer tumor cells on high proliferation capacity and progenitor-like fate through multidimensional reprogramming1–3.”

    From Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis (2024) · cites this paper as [1]

    In “The giant cell cycle as a novel mechanism for somatic cell dedifferentiation (or reprogramming)” (page unavailable), the paper proposes that somatic-cell dedifferentiation during tumor initiation can produce embryonic-like cancer stem cells. It does not establish the claim specifically for epithelial cells or say that dedifferentiation confers high proliferation capacity; its mechanism is presented as a proposal rather than a recognized general transition. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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  1. [1]Weinberg RA, Coming full circle-from endless complexity to simplicity and back again, Cell 157 (1) (2014) 267– 271. 24679541
  2. [2]Nowell PC, The clonal evolution of tumor cell populations, Science 194 (4260) (1976) 23– 28. 959840
  3. [3]McGranahan N, Swanton C, Clonal heterogeneity and tumor evolution: past, present, and the future, Cell 168 (4) (2017) 613– 628. 28187284
  4. [5]Kumar V, Abbas AK, Fausto N, Aster J, Robbins and Contran Pathologic Basis of Disease, Sauders Elsevier, 2010, pp. 262– 270 Chapter 7.
  5. [6]Willis RA, Pathology of Tumors, 4th edition, Butterworth & Co. Ltd, 1967.
  6. [7]Sadler T, Langman’s Medical Embryology, 12th edition, Lippincott Willians & Wilkins, 2012 (Chapter 3, p37).
  7. [8]Hemberger M, Dean W, Reik W, Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington’s canal, Nat. Rev. Mol. Cell Biol. 10 (8) (2009) 526– 537. 19603040
  8. [9]Turner S, Wong HP, Rai J, Hartshorne GM, Telomere lengths in human oocytes, cleavage stage embryos and blastocysts, Mol. Hum. Reprod 16 (9) (2010) 685– 694. 20573647 PMC2930518
  9. [10]Ledbetter DH, Chaos in the embryo, Nat. Med 15 (5) (2009) 490– 491. 19424206
  10. [11]Chazaud C, Yamanaka Y, Lineage specification in the mouse preimplantation embryo, Development 143 (7) (2016) 1063– 1074. 27048685
  11. [13]Rivron NC, Frias-Aldeguer J, Vrij EJ, Boisset JC, Korving J, Vivie J, Truckenmuller RK, van Oudenaarden A, van Blitterswijk CA, Geijsen N, Blastocyst-like structures generated solely from stem cells, Nature 557 (7703) (2018) 106– 111. 29720634
  12. [14]Takahashi K, Yamanaka S, Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors, Cell 126 (4) (2006) 663– 676. 16904174
  13. [15]Gurdon JB, Elsdale TR, Fischberg M, Sexually mature individuals of Xenopus laevis from the transplantation of single somatic nuclei, Nature 182 (4627) (1958) 64– 65. 13566187
  14. [16]Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH, Viable offspring derived from fetal and adult mammalian cells, Nature 385 (6619) (1997) 810– 813. 9039911
  15. [17]Liu Z, Cai Y, Wang Y, Nie Y, Zhang C, Xu Y, Zhang X, Lu Y, Wang Z, Poo M, Sun Q, Cloning of macaque monkeys by somatic cell nuclear transfer, Cell 172 (4) (2018) 881– 887 e7. 29395327
  16. [18]Abad M, Mosteiro L, Pantoja C, Canamero M, Rayon T, Ors I, Grana O, Megias D, Dominguez O, Martinez D, Manzanares M, Ortega S, Serrano M, Reprogramming in vivo produces teratomas and iPS cells with totipotency features, Nature 502 (7471) (2013) 340– 345. 24025773
  17. [20]Mosteiro L, Pantoja C, Alcazar N, Marion RM, Chondronasiou D, Rovira M, Fernandez-Marcos PJ, Munoz-Martin M, Blanco-Aparicio C, Pastor J, Gomez-Lopez G, De Martino A, Blasco MA, Abad M, Serrano M, Tissue damage and senescence provide critical signals for cellular reprogramming in vivo, Science 354 (6315) (2016). 27884981
  18. [21]Kurman RJ, Carcangiu ML, Herrington CS, Young RH, WHO Classification of Tumours of Female Reproductive Organ, 4th edition, Publisher: International Agency for Reseach on Cancer (IARC), Lyon, 2014 2014.
  19. [26]Bignold LP, Coghlan BL, Jersmann HP, Hansemann, Boveri, chromosomes and the gametogenesis-related theories of tumours, Cell Biol. Int 30 (7) (2006) 640– 644. 16753311
  20. [27]Bignold LP, Coghlan B, Jersmann H, David Paul Hansemann: chromosomes and the origin of the cancerous features of tumor cells, Cell. Oncol 31 (1) (2009) 61. 19096152 PMC4618563
  21. [30]Maehle AH, Ambiguous cells: the emergence of the stem cell concept in the nineteenth and twentieth centuries, Notes Rec. R. Soc. Lond 65 (4) (2011) 359– 378. 22332468 PMC3793240
  22. [32]Stevens LC, Little CC, Spontaneous testicular teratomas in an inbred strain of mice, Proc. Natl. Acad. Sci. U. S. A 40 (11) (1954) 1080– 1087. 16578442 PMC1063969
  23. [33]Stevens LC, Experimental production of testicular teratomas in mice, Proc. Natl. Acad. Sci. U. S. A 52 (1964) 654– 661. 14212538 PMC300322
  24. [34]Kleinsmith LJ, Pierce GB Jr., Multipotentiality of single embryonal carcinoma cells, Cancer Res 24 (1964) 1544– 1551. 14234000
  25. [35]Pierce GB, Speers WC, Tumors as caricatures of the process of tissue renewal: prospects for therapy by directing differentiation, Cancer Res 48 (8) (1988) 1996– 2004. 2450643
  26. [36]Pierce GB, Nakane PK, Martinez-Hernandez A, Ward JM, Ultrastructural comparison of differentiation of stem cells of murine adenocarcinomas of colon and breast with their normal counterparts, J. Natl. Cancer Inst 58 (5) (1977) 1329– 1345. 857028
  27. [37]Pierce GB, Wallace C, Differentiation of malignant to benign cells, Cancer Res 31 (2) (1971) 127– 134. 5545265
  28. [38]Sell S, Pierce GB, Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas and epithelial cancers, Lab. Invest 70 (1) (1994) 6– 22. 8302019
  29. [39]Sell S, On the stem cell origin of cancer, Am. J. Pathol 176 (6) (2010) 2584– 494. 20431026 PMC2877820
  30. [40]Mintz B, Illmensee K, Normal genetically mosaic mice produced from malignant teratocarcinoma cells, Proc. Natl. Acad. Sci. U. S. A 72 (9) (1975) 3585– 3589. 1059147 PMC433040
  31. [41]Illmensee K, Mintz B, Totipotency and normal differentiation of single teratocarcinoma cells cloned by injection into blastocysts, Proc. Natl. Acad. Sci. U. S. A 73 (2) (1976) 549– 553. 1061157 PMC335947
  32. [43]Mintz B, Cronmiller C, Custer RP, Somatic cell origin of teratocarcinomas, Proc. Natl. Acad. Sci. U. S. A 75 (6) (1978) 2834– 2838. 275854 PMC392659
  33. [44]Soto AM, Sonnenschein C, Emergentism as a default: cancer as a problem of tissue organization, J. Biosci 30 (1) (2005) 103– 118. 15824446
  34. [45]Baker SG, A cancer theory kerfuffle can lead to new lines of research, J. Natl. Cancer Inst 107 (2) (2015). PMC4326310 25528755
  35. [46]Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ, Cancer/testis antigens, gametogenesis and cancer. Nature reviews, Cancer 5 (8) (2005) 615– 625. 16034368
  36. [47]Old LJ, Cancer is a somatic cell pregnancy, Cancer Immun 7 (2007) 19. 17983204 PMC2935741
  37. [48]Vinnitsky V, The development of a malignant tumor is due to a desperate asexual self-cloning process in which cancer stem cells develop the ability to mimic the genetic program of germline cells, Intrinsically Disord. Proteins 2 (1) (2014) e29997. PMC5314931 28232878
  38. [49]Erenpreisa J, Salmina K, Huna A, Jackson TR, Vazquez-Martin A, Cragg MS, The “virgin birth”, polyploidy, and the origin of cancer, Oncoscience 2 (1) (2015) 3– 14. 25821840 PMC4341460
  39. [50]Ratajczak MZ, Shin DM, Kucia M, Very small embryonic/epiblast-like stem cells: a missing link to support the germ line hypothesis of cancer development? Am. J. Pathol 174 (6) (2009) 1985– 1992. 19406990 PMC2684162
  40. [51]Liu C, Xu S, Ma Z, Zeng Y, Chen Z, Lu Y, Generation of pluripotent cancer-initiating cells from transformed bone marrow-derived cells, Cancer Lett 303 (2) (2011) 140– 149. 21339043
  41. [52]Liu C, Ma Z, Xu S, Hou J, Hu Y, Yu Y, Liu R, Chen Z, Lu Y, Activation of the germ-cell potential of human bone marrow-derived cells by a chemical carcinogen, Sci. Rep 4 (2014) 5564. 24998261 PMC4083294
  42. [53]Liu C, Ma Z, Hou J, Zhang H, Liu R, Wu W, Liu W, Lu Y, Germline traits of human hepatoblastoma cells associated with growth and metastasis, Biochem. Biophys. Res. Commun 437 (1) (2013) 120– 126. 23800414
  43. [54]Becker AJ, Mc CE, Till JE, Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells, Nature 197 (1963) 452– 454. 13970094
  44. [55]Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Cacerescortes J, Minden M, Paterson B, Caligiuri MA, Dick JE, A cell initiating human acute myeloid-leukemia after transplantation into scid mice, Nature 367 (6464) (1994) 645– 648. 7509044
  45. [56]Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, Visvader J, Weissman IL, Wahl GM, Cancer stem cells–perspectives on current status and future directions: AACR workshop on cancer stem cells, Cancer Res 66 (19) (2006) 9339– 9344. 16990346
  46. [57]Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ, Efficient tumour formation by single human melanoma cells, Nature 456 (7222) (2008) 593– 598. 19052619 PMC2597380
  47. [58]Quintana E, Shackleton M, Foster HR, Fullen DR, Sabel MS, Johnson TM, Morrison SJ, Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is reversible and not hierarchically organized, Cancer Cell 18 (5) (2010) 510– 523. 21075313 PMC3031091
  48. [59]Meacham CE, Morrison SJ, Tumour heterogeneity and cancer cell plasticity, Nature 501 (7467) (2013) 328– 337. 24048065 PMC4521623
  49. [60]Kreso A, Dick JE, Evolution of the cancer stem cell model, Cell Stem Cell 14 (3) (2014) 275– 291. 24607403
  50. [61]Nguyen LV, Vanner R, Dirks P, Eaves CJ, Cancer stem cells: an evolving concept. Nature reviews, Cancer 12 (2) (2012) 133– 143. 22237392
  51. [62]Batlle E, Clevers H, Cancer stem cells revisited, Nat. Med 23 (2017) 1124. 28985214
  52. [63]Beck B, Blanpain C, Unravelling cancer stem cell potential. Nature reviews, Cancer 13 (10) (2013) 727– 738. 24060864
  53. [64]Blanpain C, Simons BD, Unravelling stem cell dynamics by lineage tracing, Nat. Rev. Mol. Cell Biol 14 (8) (2013) 489– 502. 23860235
  54. [65]Yang T, Rycaj K, Liu ZM, Tang DG, Cancer stem cells: constantly evolving and functionally heterogeneous therapeutic targets, Cancer Res 74 (11) (2014) 2922– 2927. 24713433 PMC4112560
  55. [66]Maenhaut C, Dumont JE, Roger PP, van Staveren WC, Cancer stem cells: a reality, a myth, a fuzzy concept or a misnomer? An analysis, Carcinogenesis 31 (2) (2010) 149– 158. 19858069
  56. [67]Antoniou A, Hebrant A, Dom G, Dumont JE, Maenhaut C, Cancer stem cells, a fuzzy evolving concept: a cell population or a cell property? Cell Cycle 12 (24) (2013) 3743– 3748. 24270846 PMC3905066
  57. [68]Niu N, Mercado-Uribe I, Liu J, Dedifferentiation into blastomere-like cancer stem cells via formation of polyploid giant cancer cells, Oncogene 36 (2017) 4887. 28436947 PMC5582213
  58. [69]Orr-Weaver TL, When bigger is better: the role of polyploidy in organogenesis, Trends Genet 31 (6) (2015) 307– 315. 25921783 PMC4537166
  59. [70]Scholes DR, Paige KN, Plasticity in ploidy: a generalized response to stress, Trends Plant Sci 20 (3) (2015) 165– 175. 25534217
  60. [71]Fox DT, Duronio RJ, Endoreplication and polyploidy: insights into development and disease, Development 140 (1) (2013) 3– 12. 23222436 PMC3513989
  61. [72]Edgar BA, Zielke N, Gutierrez C, Endocycles: a recurrent evolutionary innovation for post-mitotic cell growth, Nat. Rev. Mol. Cell Biol 15 (3) (2014) 197– 210. 24556841
  62. [73]Comai L, The advantages and disadvantages of being polyploid, Nat. Rev. Genet 6 (11) (2005) 836– 846. 16304599
  63. [74]Carbone L, Chavez SL, Mammalian pre-implantation chromosomal instability: species comparison, evolutionary considerations, and pathological correlations, Syst. Biol. Reprod. Med 61 (6) (2015) 321– 335. 26366555 PMC7857118
  64. [75]Niakan KK, Han J, Pedersen RA, Simon C, Pera RA, Human pre-implantation embryo development, Development 139 (5) (2012) 829– 841. 22318624 PMC3274351
  65. [76]Kligman I, Benadiva C, Alikani M, Munne S, The presence of multinucleated blastomeres in human embryos is correlated with chromosomal abnormalities, Hum. Reprod 11 (7) (1996) 1492– 1498. 8671491
  66. [77]Pickering SJ, Taylor A, Johnson MH, Braude PR, An analysis of multi-nucleated blastomere formation in human embryos, Hum. Reprod 10 (7) (1995) 1912– 1922. 8583010
  67. [78]Vanneste E, Voet T, Le Caignec C, Ampe M, Konings P, Melotte C, Debrock S, Amyere M, Vikkula M, Schuit F, Fryns JP, Verbeke G, D’Hooghe T, Moreau Y, Vermeesch JR, Chromosome instability is common in human cleavage-stage embryos, Nat. Med 15 (5) (2009) 577– 583. 19396175
  68. [79]Vera-Rodriguez M, Chavez SL, Rubio C, Reijo Pera RA, Simon C, Prediction model for aneuploidy in early human embryo development revealed by single-cell analysis, Nat. Commun 6 (2015) 7601. 26151134 PMC4506544
  69. [80]Reichmann J, Nijmeijer B, Hossain MJ, Eguren M, Schneider I, Politi AZ, Roberti MJ, Hufnagel L, Hiiragi T, Ellenberg J, Dual-spindle formation in zygotes keeps parental genomes apart in early mammalian embryos, Science 361 (6398) (2018) 189– 193. 30002254
  70. [81]Daughtry BL, Chavez SL, Chromosomal instability in mammalian pre-implantation embryos: potential causes, detection methods, and clinical consequences, Cell Tissue Res 363 (1) (2016) 201– 225. 26590822 PMC5621482
  71. [82]Levan A, Hauschka TS, Endomitotic reduplication mechanisms in ascites tumors of the mouse, J. Natl. Cancer Inst 14 (1) (1953) 1– 43. 13097135
  72. [83]Zack TI, Schumacher SE, Carter SL, Cherniack AD, Saksena G, Tabak B, Lawrence MS, Zhang CZ, Wala J, Mermel CH, Sougnez C, Gabriel SB, Hernandez B, Shen H, Laird PW, Getz G, Meyerson M, Beroukhim R, Pan-cancer patterns of somatic copy number alteration, Nat. Genet 45 (10) (2013) 1134– 1140. 24071852 PMC3966983
  73. [84]Barrett MT, Pritchard D, Palanca-Wessels C, Anderson J, Reid BJ, Rabinovitch PS, Molecular phenotype of spontaneously arising 4N (G2-tetraploid) intermediates of neoplastic progression in Barrett’s esophagus, Cancer Res 63 (14) (2003) 4211– 4217. 12874028
  74. [85]McCluggage WG, Lyness RW, Atkinson RJ, Dobbs SP, Harley I, McClelland HR, Price JH, Morphological effects of chemotherapy on ovarian carcinoma, J. Clin. Pathol 55 (1) (2002) 27– 31. 11825920 PMC1769574
  75. [86]Illidge TM, Cragg MS, Fringes B, Olive P, Erenpreisa JA, Polyploid giant cells provide a survival mechanism for p53 mutant cells after DNA damage, Cell Biol. Int 24 (9) (2000) 621– 633. 10964452
  76. [87]Wang Y, Wang Y, Zheng W, Cytologic changes of ovarian epithelial cancer induced by neoadjuvant chemotherapy, Int. J. Clin. Exp. Pathol 6 (10) (2013) 2121– 2128. 24133590 PMC3796234
  77. [88]Zhang L, Ding P, Lv H, Zhang D, Liu G, Yang Z, Li Y, Liu J, Zhang S, Number of polyploid giant cancer cells and expression of EZH2 are associated with VM formation and tumor grade in human ovarian tumor, Biomed Res. Int (2014) 903542 2014. 25025074 PMC4082869
  78. [89]Qu Y, Zhang L, Rong Z, He T, Zhang S, Number of glioma polyploid giant cancer cells (PGCCs) associated with vasculogenic mimicry formation and tumor grade in human glioma, J. Exp. Clin. Cancer Res 32 (2013) 75. PMC4029228 24422894
  79. [90]Fei F, Zhang D, Yang Z, Wang S, Wang X, Wu Z, Wu Q, Zhang S, The number of polyploid giant cancer cells and epithelial-mesenchymal transition-related proteins are associated with invasion and metastasis in human breast cancer, J. Exp. Clin. Cancer Res 34 (1) (2015) 158. PMC4690326 26702618
  80. [91]Mu Z, Wang C, Ye Z, Rossi G, Sun C, Li L, Zhu Z, Yang H, Cristofanilli M, Prognostic values of cancer associated macrophage-like cells (CAML) enumeration in metastatic breast cancer, Breast Cancer Res. Treat 165 (3) (2017) 733– 741. 28687903
  81. [92]Clawson GA, Matters GL, Xin P, Imamura-Kawasawa Y, Du Z, Thiboutot DM, Helm KF, Neves RI, Abraham T, Macrophage-tumor cell fusions from peripheral blood of melanoma patients, PLoS One 10 (8) (2015) e0134320. 26267609 PMC4534457
  82. [93]Liu H, Sun B, Wang S, Liu C, Lu Y, Li D, Liu X, Circulating tumor cells as a biomarker in pancreatic ductal adenocarcinoma, Cell. Physiol. Biochem 42 (1) (2017) 373– 382. 28558380
  83. [94]Rantala JK, Edgren H, Lehtinen L, Wolf M, Kleivi K, Vollan HK, Aaltola AR, Laasola P, Kilpinen S, Saviranta P, Iljin K, Kallioniemi O, Integrative functional genomics analysis of sustained polyploidy phenotypes in breast cancer cells identifies an oncogenic profile for GINS2, Neoplasia (New York N.Y.) 12 (11) (2010) 877– 888. PMC2981730 21082043
  84. [95]Vitale I, Galluzzi L, Senovilla L, Criollo A, Jemaa M, Castedo M, Kroemer G, Illicit survival of cancer cells during polyploidization and depolyploidization, Cell Death Differ 18 (9) (2011) 1403– 1413. 21072053 PMC3178421
  85. [96]Walen KH, Human diploid fibroblast cells in senescence; cycling through polyploidy to mitotic cells, In Vitro Cell. Dev. Biol. Anim 42 (7) (2006) 216– 224. 16948503
  86. [97]Vakifahmetoglu H, Olsson M, Zhivotovsky B, Death through a tragedy: mitotic catastrophe, Cell Death Differ 15 (7) (2008) 1153– 1162. 18404154
  87. [98]Ganem NJ, Storchova Z, Pellman D, Tetraploidy, aneuploidy and cancer, Curr. Opin. Genet. Dev 17 (2) (2007) 157– 162. 17324569
  88. [99]Ganem NJ, Pellman D, Limiting the proliferation of polyploid cells, Cell 131 (3) (2007) 437– 440. 17981108
  89. [100]Wen Q, Goldenson B, Silver SJ, Schenone M, Dancik V, Huang Z, Wang LZ, Lewis TA, An WF, Li X, Bray MA, Thiollier C, Diebold L, Gilles L, Vokes MS, Moore CB, Bliss-Moreau M, Verplank L, Tolliday NJ, Mishra R, Vemula S, Shi J, Wei L, Kapur R, Lopez CK, Gerby B, Ballerini P, Pflumio F, Gilliland DG, Goldberg L, Birger Y, Izraeli S, Gamis AS, Smith FO, Woods WG, Taub J, Scherer CA, Bradner JE, Goh BC, Mercher T, Carpenter AE, Gould RJ, Clemons PA, Carr SA, Root DE, Schreiber SL, Stern AM, Crispino JD, Identification of regulators of polyploidization presents therapeutic targets for treatment of AMKL, Cell 150 (3) (2012) 575– 589. 22863010 PMC3613864
  90. [101]Ewald JA, Desotelle JA, Wilding G, Jarrard DF, Therapy-induced senescence in cancer, J. Natl. Cancer Inst 102 (20) (2010) 1536– 1546. 20858887 PMC2957429
  91. [103]Ganem NJ, Cornils H, Chiu SY, O’Rourke KP, Arnaud J, Yimlamai D, Thery M, Camargo FD, Pellman D, Cytokinesis failure triggers hippo tumor suppressor pathway activation, Cell 158 (4) (2014) 833– 848. 25126788 PMC4136486
  92. [104]Solari F, Domenget C, Gire V, Woods C, Lazarides E, Rousset B, Jurdic P, Multinucleated cells can continuously generate mononucleated cells in the absence of mitosis: a study of cells of the avian osteoclast lineage, J. Cell. Sci 108 (10) (1995) 3233– 3241. 7593284
  93. [105]Erenpreisa JA, Cragg MS, Fringes B, Sharakhov I, Illidge TM, Release of mitotic descendants by giant cells from irradiated Burkitt’s lymphoma cell line, Cell Biol. Int 24 (9) (2000) 635– 648. 10964453
  94. [106]Sundaram M, Guernsey DL, Rajaraman MM, Rajaraman R, Neosis: a novel type of cell division in cancer, Cancer Biol. Ther 3 (2) (2004) 207– 218. 14726689
  95. [107]Walen KH, Spontaneous cell transformation: karyoplasts derived from multi-nucleated cells produce new cell growth in senescent human epithelial cell cultures, In Vitro Cell. Dev. Biol.- Anim 40 (5–6) (2004) 150– 158. 15479119
  96. [108]Walen KH, The origin of transformed cells: studies of spontaneous and induced cell transformation in cell cultures from marsupials, a snail, and human amniocytes, Cancer Genet. Cytogenet 133 (1) (2002) 45– 54. 11890989
  97. [109]Zhang S, Mercado-Uribe I, Xing Z, Sun B, Kuang J, Liu J, Generation of cancer stem-like cells through the formation of polyploid giant cancer cells, Oncogene 33 (1) (2014) 116– 128. 23524583 PMC3844126
  98. [110]Weihua Z, Lin Q, Ramoth AJ, Fan D, Fidler IJ, Formation of solid tumors by a single multinucleated cancer cell, Cancer 117 (17) (2011) 4092– 4099. 21365635 PMC3136613
  99. [111]Rohnalter V, Roth K, Finkernagel F, Adhikary T, Obert J, Dorzweiler K, Bensberg M, Muller-Brusselbach S, Muller R, A multi-stage process including transient polyploidization and EMT precedes the emergence of chemoresistent ovarian carcinoma cells with a dedifferentiated and pro-inflammatory secretory phenotype, Oncotarget (2015). PMC4741876 26503466
  100. [112]Puig PE, Guilly MN, Bouchot A, Droin N, Cathelin D, Bouyer F, Favier L, Ghiringhelli F, Kroemer G, Solary E, Martin F, Chauffert B, Tumor cells can escape DNA-damaging cisplatin through DNA endoreduplication and reversible polyploidy, Cell Biol. Int 32 (9) (2008) 1031– 1043. 18550395
  101. [113]Niu N, Zhang J, Zhang N, Mercado-Uribe I, Tao F, Han Z, Pathak S, Multani AS, Kuang J, Yao J, Bast RC, Sood AK, Hung MC, Liu J, Linking genomic reorganization to tumor initiation via the giant cell cycle, Oncogenesis 5 (12) (2016) e281. 27991913 PMC5177773
  102. [114]Mirzayans R, Andrais B, Scott A, Wang YW, Kumar P, Murray D, Multinucleated giant cancer cells produced in response to ionizing radiation retain viability and replicate their genome, Int. J. Mol. Sci 18 (2) (2017). PMC5343895 28208747
  103. [115]Díaz-Carballo D, Saka S, Klein J, Rennkamp T, Acikelli AH, Malak S, Jastrow H, Wennemuth G, Tempfer C, Schmitz I, Tannapfel A, Strumberg D, A distinct oncogenerative multinucleated cancer cell serves as a source of stemness and tumor heterogeneity, Cancer Res 78 (9) (2018) 2318– 2331. 29440172
  104. [116]Zheng L, Dai H, Zhou M, Li X, Liu C, Guo Z, Wu X, Wu J, Wang C, Zhong J, Huang Q, Garcia-Aguilar J, Pfeifer GP, Shen B, Polyploid cells rewire DNA damage response networks to overcome replication stress-induced barriers for tumour progression, Nat. Commun 3 (2012) 815. 22569363 PMC3517178
  105. [117]Leikam C, Hufnagel AL, Otto C, Murphy DJ, Muhling B, Kneitz S, Nanda I, Schmid M, Wagner TU, Haferkamp S, Brocker EB, Schartl M, Meierjohann S, In vitro evidence for senescent multinucleated melanocytes as a source for tumor-initiating cells, Cell Death Dis 6 (2015) e1711. 25837487 PMC4650540
  106. [118]Fujiwara T, Bandi M, Nitta M, Ivanova EV, Bronson RT, Pellman D, Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells, Nature 437 (7061) (2005) 1043– 1047. 16222300
  107. [119]Davoli T, de Lange T, The causes and consequences of polyploidy in normal development and cancer, Annu. Rev. Cell Dev. Biol 27 (2011) 585– 610. 21801013
  108. [120]Vitale I, Senovilla L, Jemaa M, Michaud M, Galluzzi L, Kepp O, Nanty L, Criollo A, Rello-Varona S, Manic G, Metivier D, Vivet S, Tajeddine N, Joza N, Valent A, Castedo M, Kroemer G, Multipolar mitosis of tetraploid cells: inhibition by p53 and dependency on Mos, EMBO J 29 (7) (2010) 1272– 1284. 20186124 PMC2857458
  109. [121]Erenpreisa J, Salmina K, Huna A, Kosmacek EA, Cragg MS, Ianzini F, Anisimov AP, Polyploid tumour cells elicit paradiploid progeny through depolyploidizing divisions and regulated autophagic degradation, Cell Biol. Int 35 (7) (2011) 687– 695. 21250945
  110. [122]Mittal K, Donthamsetty S, Kaur R, Yang C, Gupta MV, Reid MD, Choi DH, Rida PCG, Aneja R, Multinucleated polyploidy drives resistance to docetaxel chemotherapy in prostate cancer, Br. J. Cancer 116 (2017) 1186. 28334734 PMC5418452
  111. [123]Dewhurst SM, McGranahan N, Burrell RA, Rowan AJ, Grönroos E, Endesfelder D, Joshi T, Mouradov D, Gibbs P, Ward RL, Hawkins NJ, Szallasi Z, Sieber OM, Swanton C, Tolerance of whole-genome doubling propagates chromosomal instability and accelerates Cancer genome evolution, Cancer Discov 4 (2) (2014) 175– 185. 24436049 PMC4293454
  112. [124]Mirzayans R, Andrais B, Murray D, Roles of polyploid/multinucleated giant cancer cells in metastasis and diesease relapse following anticancer treatment, Cancers 10 (4) (2018). PMC5923373 29662021
  113. [125]Ogden A, Rida PC, Reid MD, Kucuk O, Aneja R, Die-hard survivors: heterogeneity in apoptotic thresholds may underlie chemoresistance, Expert Rev. Anticancer Ther 15 (3) (2015) 277– 281. 25695344 PMC4457617
  114. [126]Ogden A, Rida PC, Knudsen BS, Kucuk O, Aneja R, Docetaxel-induced polyploidization may underlie chemoresistance and disease relapse, Cancer Lett 367 (2) (2015) 89– 92. 26185000 PMC4813805
  115. [127]Zhang D, Yang X, Yang Z, Fei F, Li S, Qu J, Zhang M, Li Y, Zhang X, Zhang S, Daughter cells and erythroid cells budding from PGCCs and their clinicopathological significances in colorectal cancer, J. Cancer 8 (3) (2017) 469– 478. 28261349 PMC5332899
  116. [128]Erenpreisa J, Kalejs M, Cragg MS, Mitotic catastrophe and endomitosis in tumour cells: an evolutionary key to a molecular solution, Cell Biol. Int 29 (12) (2005) 1012– 1018. 16310380
  117. [129]Tamori Y, Deng WM, Tissue repair through cell competition and compensatory cellular hypertrophy in postmitotic epithelia, Dev. Cell 25 (4) (2013) 350– 363. 23685249 PMC3891806
  118. [130]Gentric G, Desdouets C, Polyploidization in liver tissue, Am. J. Pathol 184 (2) (2014) 322– 331. 24140012
  119. [131]Lucchetta EM, Ohlstein B, Amitosis of polyploid cells regenerates functional stem cells in the Drosophila intestine, Cell Stem Cell 20 (5) (2017) 609– 620 e6. 28343984 PMC5419863
  120. [132]Cong B, Ohsawa S, Igaki T, JNK and Yorkie drive tumor progression by generating polyploid giant cells in Drosophila, Oncogene 37 (23) (2018) 3088– 3097. 29535423
  121. [133]Boroviak T, Nichols J, The birth of embryonic pluripotency, Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci 369 (1657) (2014). PMC4216464 25349450
  122. [134]Munoz-Espin D, Serrano M, Cellular senescence: from physiology to pathology, Nat. Rev. Mol. Cell Biol 15 (7) (2014) 482– 496. 24954210
  123. [136]Raghuram GV, Gupta D, Subramaniam S, Gaikwad A, Khare NK, Nobre M, Nair NK, Mittal I, Physical shearing imparts biological activity to DNA and ability to transmit itself horizontally across species and kingdom boundaries, BMC Mol. Biol 18 (1) (2017) 21. 28793862 PMC5550992
  124. [137]Noubissi FK, Ogle BM, Cancer cell fusion: mechanisms slowly unravel, Int. J. Mol. Sci 17 (9) (2016). PMC5037852 27657058
  125. [138]Bastida-Ruiz D, Van Hoesen K, Cohen M, The dark side of cell fusion, Int. J. Mol. Sci 17 (5) (2016). PMC4881464 27136533
  126. [139]Rengstl B, Newrzela S, Heinrich T, Weiser C, Thalheimer FB, Schmid F, Warner K, Hartmann S, Schroeder T, Kuppers R, Rieger MA, Hansmann ML, Incomplete cytokinesis and re-fusion of small mononucleated Hodgkin cells lead to giant multinucleated Reed-Sternberg cells, Proc. Natl. Acad. Sci. U. S. A 110 (51) (2013) 20729– 20734. 24302766 PMC3870723
  127. [140]Pellestor F, Gatinois V, Puechberty J, Genevieve D, Lefort G, Chromothripsis: potential origin in gametogenesis and preimplantation cell divisions. A review, Fertil. Steril 102 (6) (2014) 1785– 1796. 25439810
  128. [141]Zhang S, Mercado-Uribe I, Sood A, Bast RC, Liu J, Coevolution of neoplastic epithelial cells and multilineage stroma via polyploid giant cells during immortalization and transformation of mullerian epithelial cells, Genes Cancer 7 (3–4) (2016) 60– 72. 27382431 PMC4918945
  129. [142]Zhang S, Mercado-Uribe I, Liu J, Tumor stroma and differentiated cancer cells can be originated directly from polyploid giant cancer cells induced by paclitaxel, Int. J. Cancer 134 (3) (2014) 508– 518. 23754740 PMC4175522
  130. [143]Zhang S, Mercado-Uribe I, Liu J, Generation of erythroid cells from fibroblasts and cancer cells in vitro and in vivo, Cancer Lett 333 (2) (2013) 205– 212. 23376638 PMC3760787
  131. [144]Jia L, Zhang S, Ye Y, Li X, Mercado-Uribe I, Bast RC Jr., J. Liu, Paclitaxel inhibits ovarian tumor growth by inducing epithelial cancer cells to benign fibroblast-like cells, Cancer Lett 326 (2) (2012) 176– 182. 22902993 PMC3495569
  132. [145]Was H, Czarnecka J, Kominek A, Barszcz K, Bernas T, Piwocka K, Kaminska B, Some chemotherapeutics-treated colon cancer cells display a specific phenotype being a combination of stem-like and senescent cell features, Cancer Biol. Ther 19 (1) (2018) 63– 75. 29053388 PMC5790359
  133. [146]Zhang S, Mercado-Uribe I, Hanash S, Liu J, iTRAQ-based proteomic analysis of polyploid giant cancer cells and budding progeny cells reveals several distinct pathways for ovarian cancer development, PLoS One 8 (11) (2013) e80120. 24348907 PMC3858113
  134. [147]Vazquez-Martin A, Anatskaya OV, Giuliani A, Erenpreisa J, Huang S, Salmina K, Inashkina I, Huna A, Nikolsky NN, Vinogradov AE, Somatic polyploidy is associated with the upregulation of c-MYC interacting genes and EMT-like signature, Oncotarget 7 (46) (2016) 75235– 75260. 27655693 PMC5342737
  135. [148]Salmina K, Jankevics E, Huna A, Perminov D, Radovica I, Klymenko T, Ivanov A, Jascenko E, Scherthan H, Cragg M, Erenpreisa J, Up-regulation of the embryonic self-renewal network through reversible polyploidy in irradiated p53-mutant tumour cells, Exp. Cell Res 316 (13) (2010) 2099– 2112. 20457152
  136. [149]Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, Weinberg RA, An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors, Nat. Genet 40 (5) (2008) 499– 507. 18443585 PMC2912221
  137. [150]Kim J, Orkin SH, Embryonic stem cell-specific signatures in cancer: insights into genomic regulatory networks and implications for medicine, Genome Med 3 (11) (2011) 75. 22126538 PMC3308030
  138. [151]Beltran AS, Rivenbark AG, Richardson BT, Yuan X, Quian H, Hunt JP, Zimmerman E, Graves LM, Blancafort P, Generation of tumor-initiating cells by exogenous delivery of OCT4 transcription factor, Breast Cancer Res.: BCR 13 (5) (2011) R94. 21952072 PMC3262206
  139. [152]Ye X, Weinberg RA, Epithelial-mesenchymal plasticity: a central regulator of Cancer progression, Trends Cell Biol 25 (11) (2015) 675– 686. 26437589 PMC4628843
  140. [153]Chaffer CL, Weinberg RA, How does multistep tumorigenesis really proceed? Cancer Discov 5 (1) (2015) 22– 24. 25583800 PMC4295623
  141. [155]Milanovic M, Fan DNY, Belenki D, Dabritz JHM, Zhao Z, Yu Y, Dorr JR, Dimitrova L, Lenze D, Monteiro Barbosa IA, Mendoza-Parra MA, Kanashova T, Metzner M, Pardon K, Reimann M, Trumpp A, Dorken B, Zuber J, Gronemeyer H, Hummel M, Dittmar G, Lee S, Schmitt CA, Senescence-associated reprogramming promotes cancer stemness, Nature 553 (7686) (2018) 96– 100. 29258294
  142. [156]Palmer NP, Schmid PR, Berger B, Kohane IS, A gene expression profile of stem cell pluripotentiality and differentiation is conserved across diverse solid and hematopoietic cancers, Genome Biol 13 (8) (2012) R71. 22909066 PMC3491371
  143. [158]Friedmann-Morvinski D, Bushong EA, Ke E, Soda Y, Marumoto T, Singer O, Ellisman MH, Verma IM, Dedifferentiation of neurons and astrocytes by onco-genes can induce gliomas in mice, Science 338 (6110) (2012) 1080– 1084. 23087000 PMC3595315
  144. [159]Suva ML, Rheinbay E, Gillespie SM, Patel AP, Wakimoto H, Rabkin SD, Riggi N, Chi AS, Cahill DP, Nahed BV, Curry WT, Martuza RL, Rivera MN, Rossetti N, Kasif S, Beik S, Kadri S, Tirosh I, Wortman I, Shalek AK, Rozenblatt-Rosen O, Regev A, Louis DN, Bernstein BE, Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells, Cell 157 (3) (2014) 580– 594. 24726434 PMC4004670
  145. [160]Goding CR, Pei D, Lu X, Cancer: pathological nuclear reprogramming? Nature reviews, Cancer 14 (8) (2014) 568– 573. 25030952
  146. [161]Vincent M, Cancer: a de-repression of a default survival program common to all cells?: a life-history perspective on the nature of cancer, BioEssays 34 (1) (2012) 72– 82. 22105565
  147. [162]Lineweaver CH, Davies PC, Vincent MD, Targeting cancer’s weaknesses (not its strengths): therapeutic strategies suggested by the atavistic model, BioEssays 36 (9) (2014) 827– 835. 25043755 PMC4282648
  148. [163]Trigos AS, Pearson RB, Papenfuss AT, Goode DL, Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors, Proc. Natl. Acad. Sci. U. S. A 114 (24) (2017) 6406– 6411. 28484005 PMC5474804
  149. [164]Chavez SL, Loewke KE, Han J, Moussavi F, Colls P, Munne S, Behr B, Reijo Pera RA, Dynamic blastomere behaviour reflects human embryo ploidy by the four-cell stage, Nat. Commun 3 (2012) 1251. 23212380 PMC3535341
  150. [165]Grow EJ, Flynn RA, Chavez SL, Bayless NL, Wossidlo M, Wesche DJ, Martin L, Ware CB, Blish CA, Chang HY, Pera RA, Wysocka J, Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells, Nature 522 (7555) (2015) 221– 225. 25896322 PMC4503379
  151. [166]Zhang CZ, Spektor A, Cornils H, Francis JM, Jackson EK, Liu S, Meyerson M, Pellman D, Chromothripsis from DNA damage in micronuclei, Nature 522 (7555) (2015) 179– 184. 26017310 PMC4742237
  152. [167]Zhang CZ, Leibowitz ML, Pellman D, Chromothripsis and beyond: rapid genome evolution from complex chromosomal rearrangements, Genes Dev 27 (23) (2013) 2513– 2530. 24298051 PMC3861665
  153. [168]Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, Morsberger LA, Iacobuzio-Donahue C, Follows GA, Green AR, Flanagan AM, Stratton MR, Futreal PA, Campbell PJ, Massive genomic rearrangement acquired in a single catastrophic event during cancer development, Cell 144 (1) (2011) 27– 40. 21215367 PMC3065307
  154. [169]Neiman M, Beaton MJ, Hessen DO, Jeyasingh PD, Weider LJ, Endopolyploidy as a potential driver of animal ecology and evolution, Biol. Rev. Camb. Philos. Soc (2015). 26467853
  155. [170]McClintock B, The significance of responses of the genome to challenge, Science 226 (4676) (1984) 792– 801. 15739260
  156. [171]McClintock B, The origin and behavior of mutable loci in maize, Proc. Natl. Acad. Sci. U. S. A 36 (6) (1950) 344– 355. 15430309 PMC1063197
  157. [172]McClintock B, The stability of broken ends of chromosomes in Zea Mays, Genetics 26 (2) (1941) 234– 282. 17247004 PMC1209127
  158. [173]Horne SD, Chowdhury SK, Heng HH, Stress, genomic adaptation, and the evolutionary trade-off, Front. Genet 5 (2014) 92. 24795754 PMC4005935
  159. [174]Heng HH, The genome-centric concept: resynthesis of evolutionary theory, BioEssays 31 (5) (2009) 512– 525. 19334004
  160. [175]Huang S, Non-genetic heterogeneity of cells in development: more than just noise, Development 136 (23) (2009) 3853– 3862. 19906852 PMC2778736
  161. [176]Versteeg R, Cancer: tumours outside the mutation box, Nature 506 (7489) (2014) 438– 439. 24553138
  162. [178]Pierce GB, The cancer cell and its control by the embryo. Rous-Whipple award lecture, Am. J. Pathol 113 (1) (1983) 117– 124. 6312802 PMC1916304
  163. [180]Bussey KJ, Cisneros LH, Lineweaver CH, Davies PCW, Ancestral gene regulatory networks drive cancer, Proc. Natl. Acad. Sci. U. S. A 114 (24) (2017) 6160– 6162. 28584134 PMC5474827
  164. [181]Mavaddat N, Barrowdale D, Andrulis IL, Domchek SM, Eccles D, Nevanlinna H, Ramus SJ, Spurdle A, Robson M, Sherman M, Mulligan AM, Couch FJ, Engel C, McGuffog L, Healey S, Sinilnikova OM, Southey MC, Terry MB, Goldgar D, O’Malley F, John EM, Janavicius R, Tihomirova L, Hansen TV, Nielsen FC, Osorio A, Stavropoulou A, Benitez J, Manoukian S, Peissel B, Barile M, Volorio S, Pasini B, Dolcetti R, Putignano AL, Ottini L, Radice P, Hamann U, Rashid MU, Hogervorst FB, Kriege M, van der Luijt RB, Peock S, Frost D, Evans DG, Brewer C, Walker L, Rogers MT, Side LE, Houghton C, Weaver J, Godwin AK, Schmutzler RK, Wappenschmidt B. Meindl A, Kast K, Arnold N, Niederacher D, Sutter C, Deissler H, Gadzicki D, Preisler-Adams S, Varon-Mateeva R, Schonbuchner I, Gevensleben H, Stoppa-Lyonnet D, Belotti M, Barjhoux L, Isaacs C, Peshkin BN, Caldes T, de la Hoya M, Canadas C, Heikkinen T, Heikkila P, Aittomaki K, Blanco I, Lazaro C, Brunet J, Agnarsson BA, Arason A, Barkardottir RB, Dumont M, Simard J, Montagna M, Agata S, D’Andrea E, Yan M, Fox S, Rebbeck TR, Rubinstein W, Tung N, Garber JE, Wang X, Fredericksen Z, Pankratz VS, Lindor NM, Szabo C, Offit K, Sakr R, Gaudet MM, Singer CF, Tea MK, Rappaport C, Mai PL, Greene MH, Sokolenko A, Imyanitov E, Toland AE, Senter L, Sweet K, Thomassen M, Gerdes AM, Kruse T, Caligo M, Aretini P, Rantala J, von Wachenfeld A, Henriksson K, Steele L, Neuhausen SL, Nussbaum R, Beattie M, Odunsi K, Sucheston L, Gayther SA, Nathanson K, Gross J, Walsh C, Karlan B, Chenevix-Trench G, Easton DF, Antoniou AC, Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), Cancer Epidemiol. Biomark. Prevent 21 (1) (2012) 134– 147. PMC3272407 22144499
  165. [182]Feinberg AP, The key role of epigenetics in human disease prevention and mitigation, N. Engl. J. Med 378 (14) (2018) 1323– 1334. 29617578 PMC11567374
  166. [183]Sottoriva A, Kang H, Ma Z, Graham TA, Salomon MP, Zhao J, Marjoram P, Siegmund K, Press MF, Shibata D, Curtis C, A Big Bang model of human colorectal tumor growth, Nat. Genet 47 (3) (2015) 209– 216. 25665006 PMC4575589
  167. [184]Hosseini H, Obradovic MM, Hoffmann M, Harper KL, Sosa MS, Werner-Klein M, Nanduri LK, Werno C, Ehrl C, Maneck M, Patwary N, Haunschild G, Guzvic M, Reimelt C, Grauvogl M, Eichner N, Weber F, Hartkopf AD, Taran FA, Brucker SY, Fehm T, Rack B, Buchholz S, Spang R, Meister G, Aguirre-Ghiso JA, Klein CA, Early dissemination seeds metastasis in breast cancer, Nature 540 (22/29) (2016) 552– 558. 27974799 PMC5390864
  168. [185]Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S, A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns, Nature 538 (7625) (2016) 378– 382. 27732578 PMC5446075
  169. [186]Clevers H, The cancer stem cell: premises, promises and challenges, Nat. Med 17 (3) (2011) 313– 319. 21386835
  170. [187]Jiang Q, Zhang Q, Wang S, Xie S, Fang W, Liu Z, Liu J, Yao K, A fraction of CD133+ CNE2 cells is made of giant cancer cells with morphological evidence of asymmetric mitosis, J. Cancer 6 (12) (2015) 1236– 1244. 26535065 PMC4622854
  171. [188]Lambert AW, Pattabiraman DR, Weinberg RA, Emerging biological principles of metastasis, Cell 168 (4) (2017) 670– 691. 28187288 PMC5308465
  172. [189]Jolly MK, Ware KE, Gilja S, Somarelli JA, Levine H, EMT and MET: necessary or permissive for metastasis? Mol. Oncol 11 (7) (2017) 755– 769. 28548345 PMC5496498
  173. [190]Brabletz T, Kalluri R, Nieto MA, Weinberg RA, EMT in cancer. Nature reviews, Cancer 18 (2) (2018) 128– 134. 29326430
  174. [191]Simi AK, Anlas AA, Stallings-Mann M, Zhang S, Hsia M Cichon, D.C. Radisky, C.M. Nelson, A soft microenvironment protects from failure of midbody abscission and multinucleation downstream of the EMT-promoting transcription factor Snail, Cancer Res 78 (9) (2018) 2277– 2289. 29483094 PMC5932229
  175. [193]Shay JW, Wright WE, Senescence and immortalization: role of telomeres and telomerase, Carcinogenesis 26 (5) (2005) 867– 874. 15471900
  176. [194]Hahn WC, Immortalization and transformation of human cells, Mol. Cells 13 (3) (2002) 351– 361. 12132573
  177. [195]Hu J, Hwang SS, Liesa M, Gan B, Sahin E, Jaskelioff M, Ding Z, Ying H, Boutin AT, Zhang H, Johnson S, Ivanova E, Kost-Alimova M, Protopopov A, Wang YA, Shirihai OS, Chin L, DePinho RA, Antitelomerase therapy provokes ALT and mitochondrial adaptive mechanisms in cancer, Cell 148 (4) (2012) 651– 663. 22341440 PMC3286017
  178. [196]Ding Z, Wu CJ, Jaskelioff M, Ivanova E, Kost-Alimova M, Protopopov A, Chu GC, Wang G, Lu X, Labrot ES, Hu J, Wang W, Xiao Y, Zhang H, Zhang J, Gan B, Perry SR, Jiang S, Li L, Horner JW, Wang YA, Chin L, DePinho RA, Telomerase reactivation following telomere dysfunction yields murine prostate tumors with bone metastases, Cell 148 (5) (2012) 896– 907. 22341455 PMC3629723
  179. [197]Warburg O, On the origin of cancer cells, Science 123 (3191) (1956) 309– 314. 13298683
  180. [199]Seyfried TN, Cancer as a mitochondrial metabolic disease, Front. Cell Dev. Biol 3 (2015) 43. 26217661 PMC4493566
  181. [200]Braune EB, Tsoi YL, Phoon YP, Landor S, Silva Cascales H, Ramskold D, Deng Q, Lindqvist A, Lian X, Sahlgren C, Jin SB, Lendahl U, Loss of CSL unlocks a hypoxic response and enhanced tumor growth potential in breast Cancer cells, Stem Cell Rep 6 (5) (2016) 643– 651. PMC4939550 27066863
  182. [201]Kurman RJ, Shih Ie M, The dualistic model of ovarian carcinogenesis: revisited, revised, and expanded, Am. J. Pathol 186 (4) (2016) 733– 747. 27012190 PMC5808151
  183. [202]Lissa D, Senovilla L, Rello-Varona S, Vitale I, Michaud M, Pietrocola F, Boileve A, Obrist F, Bordenave C, Garcia P, Michels J, Jemaa M, Kepp O, Castedo M, Kroemer G, Resveratrol and aspirin eliminate tetraploid cells for anticancer chemoprevention, Proc. Natl. Acad. Sci. U. S. A 111 (8) (2014) 3020– 3025. 24516128 PMC3939868
  184. [203]Ohashi A, Ohori M, Iwai K, Nakayama Y, Nambu T, Morishita D, Kawamoto T, Miyamoto M, Hirayama T, Okaniwa M, Banno H, Ishikawa T, Kandori H, Iwata K, Aneuploidy generates proteotoxic stress and DNA damage concurrently with p53-mediated post-mitotic apoptosis in SAC-impaired cells, Nat. Commun 6 (2015) 7668. 26144554 PMC4506520
  185. [204]Kooreman NG, Kim Y, de Almeida PE, Termglinchan V, Diecke S, Shao NY, Wei TT, Yi H, Dey D, Nelakanti R, Brouwer TP, Paik DT, Sagiv-Barfi I, Han A, Quax PHA, Hamming JF, Levy R, Davis MM, Wu JC, Autologous iPSC-Based vaccines elicit anti-tumor responses in vivo, Cell Stem Cell 22 (4) (2018) 501– 513 e7. 29456158 PMC6134179
  186. [205]Pierce GB, Johnson LD, Differentiation and cancer, In Vitro 7 (3) (1971) 140– 145. 5163648
  187. [206]Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A, Shepherd L, Willman C, Bloomfield CD, Rowe JM, Wiernik PH, Alltrans-retinoic acid in acute promyelocytic leukemia, N. Engl. J. Med 337 (15) (1997) 1021– 1028. 9321529
  188. [207]Takahashi K, Yamanaka S, A developmental framework for induced pluripotency, Development 142 (19) (2015) 3274– 3285. 26443632
  189. [208]Hardy K, Winston RM, Handyside AH, Binucleate blastomeres in preimplantation human embryos in vitro: failure of cytokinesis during early cleavage, J. Reprod. Fertil 98 (2) (1993) 549– 558. 8410824
  190. [209]Meyer TJ, Rosenkrantz JL, Carbone L, Chavez SL, Endogenous retroviruses: with us and against us, Front. Chem 5 (2017) 23. 28439515 PMC5384584
  191. [210]Briggs SF, Dominguez AA, Chavez SL, Reijo Pera RA, Single-cell XIST expression in human preimplantation embryos and newly reprogrammed female induced pluripotent stem cells, Stem Cells 33 (6) (2015) 1771– 1781. 25753947 PMC4441606

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Authors
Liu, J.
Affiliations
The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Liu, Jinsong
ORCID
Liu, Jinsong
Venue
Seminars in Cancer Biology
Publisher
Elsevier BV
Published
2018-12
Volume
53
Pages
1-16
ISSN
1044-579X (ISSN-L)
DOI
10.1016/j.semcancer.2018.07.004
PMC
PMC6553492
OpenAlex
W2883768270
Cited by
148
References
8
Citations by year
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FWCI
1.77
Type
journal article
Language
en
Open access
Licence
Locations
  • Seminars in Cancer Biology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
Funders
University of Texas MD Anderson Cancer Center’s Ovarian Cancer SPORE
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
tumor origin, polyploid giant cancer cells, endoreplication, dedifferentiation, somatic cell reprogramming, induced pluripotent stem cells, somatic cell nuclear transfer, blastomere cleavage, embryonic development, tumor grade, cancer stem cells
MeSH terms
Blastomeres, Cell Transformation, Neoplastic, Gene Expression Regulation, Humans, Neoplasms, Polyploidy, Neoplastic Stem Cells, Giant Cells, Cell Dedifferentiation, Cellular Reprogramming

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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