title: Polyploidy: the link between senescence and cancer.
abstract: Polyploidy, a state of increased number of chromosomes, occurs often in plants and less frequently in animals. Polyploidization is recognized as a part of a developmental program and can be achieved via different mechanisms bypassing certain stages of the cell cycle. However, polyploidization also accompanies some pathological conditions as well as ageing. It is believed that tetraploid cells precede aneuploid ones in the early phases of tumor development. Division of tetraploid cells is restricted by the active tetraploid (4N G1) checkpoint. Tetraploid cells that are able to overcome this checkpoint give rise to increased genomic instability and tumor progression. Recently a cellular senescence program activated by oncogene expression was shown to act as a natural barrier against cancer development. Senescent cells were detected in many benign, but not malignant, human and animal tumors. Senescence can actually block cell transformation provided the 4N G1 checkpoint is active. Cancer cells that escaped the 4N G1 block are still able to undergo senescence upon anticancer treatment. Induction of cancer cell senescence is often correlated with high ploidy formation. Some polyploid cells can escape senescence and give progeny with numerical changes of chromosomes. Divisions of polyploid cancer cells on the road to senescence can be responsible for the ineffectiveness of anticancer therapy. Altogether, this implies polyploidy as a link between cellular senescence, cancer development and possible cancer renewal after treatment.
authors.affiliation: Laboratory of Molecular Bases of Ageing, Nencki Institute of Experimental Biology, PAS, Warsaw, Poland.
authors.forename: G
authors.initials: G
authors.lastname: Mosieniak
authors.forename: E
authors.initials: E
authors.lastname: Sikora
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D011123:Polyploidy