Rapid proliferation of daughter cells lacking particular chromosomes due to multipolar mitosis promotes clonal evolution in colorectal cancer cells

Yang, Chao; Shi, Xiaonan; Huang, Yun; Zhang, Zhen; Cooke, Howard J.; Wang, Ming-Rong; Shi, Qinghua

doi:10.4161/cc.20976

Cited by 6 publications

(4 citation statements)

References 47 publications

(88 reference statements)

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“…Chromatin instability is a major factor in the formation of tumors and shortening the length of mitosis can accelerate tumor cell proliferation [31, 32]. In our studies, we observed the localization and morphological changes of chromosomes of CRCs in various phases of mitosis after treatment with CDEs isolated from CRCs in Exo-hypoxic and Exo-normoxic condition.…”

Section: Discussionmentioning

confidence: 57%

Colon cancer cells secrete exosomes to promote self-proliferation by shortening mitosis duration and activation of STAT3 in a hypoxic environment

Ren

Sun

et al. 2019

Cell Biosci

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Colon-cancer-cell-derived exosomes (CDEs) are emerging mediators of tumorigenesis and serve as messengers of intercellular communication; however, whether the CDEs affect the proliferation of colon cancer cells themselves remains unknown. In the current study, the CDEs isolated from human colon cancer cell line SW480 and HCT116 showed a size range of 60–150 nm, typical bilayer-encapsulated vesicles, and expressed the exosomal markers CD81 and CD63. Incubation of SW480 cells with CDEs labelled with PKH67 fluorescent markers revealed that SW480 cells were able to absorb CDEs, which were mostly distributed around the nucleus. Hypoxic conditions promoted colon cancer cells to release a greater number of CDEs than normoxic conditions. MTT cell proliferation assay demonstrated CDEs promoted the proliferation of colon cancer cells in a time- and dose-dependent manner. Mechanistically, CDEs promoted colon cancer cell growth mainly through shortening mitosis duration. Meanwhile, the levels of phosphorylated STAT3 in colon cancer cells was up-regulated with the treatment of CDEs derived from hypoxic tumor cells. Our data suggests that colon cancer cells are able to promote self-growth through the secretion of exosomes, especially under hypoxic conditions, which shortens mitosis duration and activates STAT3.

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Section: Discussionmentioning

confidence: 57%

Colon cancer cells secrete exosomes to promote self-proliferation by shortening mitosis duration and activation of STAT3 in a hypoxic environment

Ren

Sun

et al. 2019

Cell Biosci

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“…Cytokinesis failure and multipolar mitosis are mechanisms that lead to aneuploidy and were observed in cultured cells from many types of cancer. Since amplifications of centro- (19). On the basis of a systematic study of Τhe Mittelman Database (15,000 karyotypes from 62 cancer classes) and the NCI and NCBI's SkY/M-FISH and CGH database (1,084 samples obtained by CGH) in terms of chromosomal aberrations, Ozery-Flato et al suggested that aneuploid cancer cells may use extra chromosome gain or loss events to restore a balance in their altered protein ratios, needed for maintaining their cellular fitness (20).…”

Section: Discussionmentioning

confidence: 99%

Cytokinesis failure and successful multipolar mitoses drive aneuploidy in glioblastoma cells

et al. 2015

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Glioblastoma (GB) is the most frequent human brain tumor and is associated with a poor prognosis. Multipolar mitosis and spindles have occasionally been observed in cultured glioblastoma cells and in glioblastoma tissues, but their mode of origin and relevance have remained unclear. In the present study, we investigated a novel GB cell line (SGB4) exhibiting mitotic aberrations and established a functional link between cytokinesis failure, centrosome amplification, multipolar mitosis and aneuploidy in glioblastoma. Long-term live cell imaging showed that >3% of mitotic SGB4 cells underwent multipolar mitosis (tripolar>tetrapolar>pentapolar). A significant amount of daugther cells generated by multipolar mitosis were viable and completed several rounds of mitosis. Pedigree analysis of mitotic events revealed that in many cases a bipolar mitosis with failed cytokinesis occurred prior to a multipolar mitosis. Additionally, we observed that SGB4 cells were also able to undergo a bipolar mitosis after failed cytokinesis. Colchicine-induced mitotic arrest and metaphase spreads demonstrated that SGB4 cells had a modal chromosome number of 58 ranging from 23 to 170. Approximately 82% of SGB4 cells were hyperdiploid (47-57 chromosomes) or hypotriploid (58-68 chromosomes). In conclusion, SGB4 cells passed through multipolar cell divisions and generated viable progeny by reductive mitoses. Our results identified cytokinesis failure occurring before and after multipolar or bipolar mitoses as important mechanisms to generate chromosomal heterogeneity in glioblastoma cells.

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“…The results generated are more representative for common chromosome segregation occurrence in cells. Our previous results have indicated that the chromosome missegregation rates for autosomes are similar in human cell lines [22, 42, 43]. In addition, chromosome specificity and brightness of FISH signals are much better than other FISH probes we tested.…”

Section: Discussionmentioning

confidence: 77%

Chromosome nondisjunction during bipolar mitoses of binucleated intermediates promote aneuploidy formation along with multipolar mitoses rather than chromosome loss in micronuclei induced by asbestos

Zhang

Huang

et al. 2016

Oncotarget

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Asbestos is a well-known occupational carcinogen that can cause aneuploidy during the early stages of neoplastic development. To explore the origins of asbestos-induced aneuploidy, we performed long-term live-cell imaging followed by fluorescence in situ hybridization of chromosomes 8 and 12 in human bronchial epithelial (HBEC) and mesothelial (MeT5A) cells. We demonstrate that asbestos induces aneuploidy via binucleated intermediates resulting from cytokinesis failure. On the one hand, asbestos increases chromosome nondisjunction during bipolar divisions of binucleated intermediates and produces near-tetraploidy. On the other hand, asbestos increases multipolar divisions of binucleated intermediates to produce aneuploidy. Surprisingly, chromosomes in asbestos-induced micronucleated cells are not truly lost by the cells, and do not contribute to aneuploid cell formation in either cell type. These results clarify the cellular source of asbestos-induced aneuploidy. In particular, they show the asbestos-induced disruption of bipolar chromosomal segregation in tetraploid cells, thereby demonstrating the causality between binucleated intermediates and aneuploidy evolution, rather than chromosome loss in micronuclei.

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Rapid proliferation of daughter cells lacking particular chromosomes due to multipolar mitosis promotes clonal evolution in colorectal cancer cells

Cited by 6 publications

References 47 publications

Colon cancer cells secrete exosomes to promote self-proliferation by shortening mitosis duration and activation of STAT3 in a hypoxic environment

Colon cancer cells secrete exosomes to promote self-proliferation by shortening mitosis duration and activation of STAT3 in a hypoxic environment

Cytokinesis failure and successful multipolar mitoses drive aneuploidy in glioblastoma cells

Chromosome nondisjunction during bipolar mitoses of binucleated intermediates promote aneuploidy formation along with multipolar mitoses rather than chromosome loss in micronuclei induced by asbestos

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