The Role of Mitotic Slippage in Creating a “Female Pregnancy-like System” in a Single Polyploid Giant Cancer Cell

Kristine Salmina (Coresponding Author), Ninel Miriam Vainshelbaum, Madara Kreishmane, Inna Inashkina, Mark Steven Cragg, Dace Pjanova, Jekaterina Erenpreisa

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


In our recent work, we observed that triple-negative breast cancer MDA-MB-231 cells respond to doxorubicin (DOX) via “mitotic slippage” (MS), discarding cytosolic damaged DNA during the process that provides their resistance to this genotoxic treatment. We also noted two populations of polyploid giant cells: those budding surviving offspring, versus those reaching huge ploidy by repeated MS and persisting for several weeks. Their separate roles in the recovery from treatment remained unclear. The current study was devoted to characterising the origin and relationship of these two sub-populations in the context of MS. MS was hallmarked by the emergence of nuclear YAP1/OCT4A/MOS/EMI2-positivity featuring a soma-germ transition to the meiotic-metaphase-arrested “maternal germ cell”. In silico, the link between modules identified in the inflammatory innate immune response to cytosolic DNA and the reproductive module of female pregnancy (upregulating placenta developmental genes) was observed in polyploid giant cells. Asymmetry of the two subnuclei types, one repairing DNA and releasing buds enriched by CDC42/ACTIN/TUBULIN and the other persisting and degrading DNA in a polyploid giant cell, was revealed. We propose that when arrested in MS, a “maternal cancer germ cell” may be parthenogenetically stimulated by the placental proto-oncogene parathyroid-hormone-like-hormone, increasing calcium, thus creating a ”female pregnancy-like” system within a single polyploid giant cancer cell.

Original languageEnglish
Article number3237
JournalInternational Journal of Molecular Sciences
Issue number4
Publication statusPublished - Jan 2023
Externally publishedYes


  • budding
  • cancer
  • female pregnancy system
  • innate immune response
  • maternal germ cell
  • mitotic slippage
  • parthenogenesis
  • placental developmental genes
  • polyploid giant cell
  • resistance to treatment
  • soma-germ transition

Field of Science*

  • 1.6 Biological sciences
  • 3.1 Basic medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database


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