Environmental stresses induce karyotypic instability in colorectal cancer cells

Tan, Zhihao; Chan, Andrew; Chua, Ying Jie Karen; Rutledge, Samuel; Pavelka, Norman; Cimini, Daniela; Rancati, Giulia

doi:10.1091/mbc.e18-10-0626

Cited by 24 publications

(25 citation statements)

References 79 publications

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“…However, conditions in the extracellular environment can increase the frequency of aberrant mitoses. Various environmental stresses can induce gene mutations or CIN [ 85 , 86 , 87 , 88 , 89 , 90 , 91 ]. The specific effects of these stresses are modulated by the nature, magnitude, and duration of the stress.…”

Section: Environmental Causes Of Karyotype Changementioning

confidence: 99%

Karyotype Aberrations in Action: The Evolution of Cancer Genomes and the Tumor Microenvironment

Baudoin

Bloomfield

2021

Genes

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Cancer is a disease of cellular evolution. For this cellular evolution to take place, a population of cells must contain functional heterogeneity and an assessment of this heterogeneity in the form of natural selection. Cancer cells from advanced malignancies are genomically and functionally very different compared to the healthy cells from which they evolved. Genomic alterations include aneuploidy (numerical and structural changes in chromosome content) and polyploidy (e.g., whole genome doubling), which can have considerable effects on cell physiology and phenotype. Likewise, conditions in the tumor microenvironment are spatially heterogeneous and vastly different than in healthy tissues, resulting in a number of environmental niches that play important roles in driving the evolution of tumor cells. While a number of studies have documented abnormal conditions of the tumor microenvironment and the cellular consequences of aneuploidy and polyploidy, a thorough overview of the interplay between karyotypically abnormal cells and the tissue and tumor microenvironments is not available. Here, we examine the evidence for how this interaction may unfold during tumor evolution. We describe a bidirectional interplay in which aneuploid and polyploid cells alter and shape the microenvironment in which they and their progeny reside; in turn, this microenvironment modulates the rate of genesis for new karyotype aberrations and selects for cells that are most fit under a given condition. We conclude by discussing the importance of this interaction for tumor evolution and the possibility of leveraging our understanding of this interplay for cancer therapy.

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Section: Environmental Causes Of Karyotype Changementioning

confidence: 99%

Karyotype Aberrations in Action: The Evolution of Cancer Genomes and the Tumor Microenvironment

Baudoin

Bloomfield

2021

Genes

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“…To study the consequence of WGD in human cells, we previously developed geneticallymatched systems of human colon cancer cell lines before and after WGD (Kuznetsova et al 2015;Tan et al 2019;Bloomfield et al 2021).…”

Section: Isogenic Human Cancer Cell Lines Reveal a Causal Relationship Between Wgd And Aneuploidy Landscapesmentioning

confidence: 99%

“…We identified distinct aneuploidy recurrence patterns and chromosome-arm genetic interactions in WGD-vs. WGD+ tumors, then validated these results in human cancer cell lines. Furthermore, we studied the relationship between WGD and aneuploidy using genetically-matched systems of human colon cancer cell lines before and after WGD (Kuznetsova et al 2015;Tan et al 2019;Bloomfield et al 2021). Our findings suggest that WGD is a major determinant of aneuploidy evolution in human cancer.…”

Section: Introductionmentioning

confidence: 99%

Whole-genome duplication shapes the aneuploidy landscape of human cancers

Prasad

Bloomfield

Levi

et al. 2021

Preprint

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Aneuploidy – a hallmark of cancer – has tissue-specific recurrence patterns suggesting it plays a driving role in cancer initiation and progression. However, the contribution of aneuploidy to tumorigenesis depends on the cellular and genomic context in which it arises. Whole-genome duplication (WGD) is a common macro-evolutionary event that occurs in >25% of human tumors during the early stages of tumorigenesis. Although tumors that have undergone WGD are reported to be more permissive to aneuploidy than tumors that have not, it remains unknown whether WGD affects aneuploidy recurrence patterns in human cancers. Here we analyzed clinical tumor samples from 449 WGD- tumors and 157 WGD+ tumors across 22 tumor types. We found distinct recurrence patterns of aneuploidy in WGD- and WGD+ tumors. The relative prevalence of recurrent aneuploidies decreased in WGD+ tumors, in line with increased aneuploidy tolerance. Moreover, the genetic interactions between chromosome arms differed between WGD- and WGD+ tumors, giving rise to distinct co-occurrence and mutual exclusivity aneuploidy patterns. The proportion of whole-chromosome aneuploidy vs. arm-level aneuploidy was significantly higher in WGD+ tumors, indicating distinct dominant mechanisms for aneuploidy formation in WGD- and WGD+ tumors. Human cancer cell lines successfully reproduced these WGD/aneuploidy interactions, confirming the relevance of studying this phenomenon in culture. Lastly, we induced WGD in human colon cancer cell lines, and followed aneuploidy formation in the isogenic WGD+/WGD-cells under standard or selective conditions. These experiments validated key findings from the clinical tumor analysis, and revealed a causal link between WGD and altered aneuploidy landscapes. We conclude that WGD shapes the aneuploidy landscape of human tumors, and propose that the interaction between WGD and aneuploidy is a major contributor to tumor evolution.

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“…Subsequent studies revealed that human cells in mitosis exposed to heat shock can result in polyploid or tetraploid cells by directly entering interphase without completing division due to the disassembled spindle and destroyed contractile ring [29,30,31]. Tan et al [32] found that that heat shock causes polyploidization of human colon carcinoma cell lines by mitotic exit without chromosome segregation. Furthermore, cytokinesis failure can generate tetraploidy that can undergo multipolar divisions and promote tumorigenesis in p53-null cancer cells [33,34].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, cell fusion is another mechanism for cancer cells to exhibit a higher degree of aneuploidy [35,36]. The above polyploid cancer cells and their aneuploid daughter cells caused by heat treatment may induce tumor heterogeneity and further drug resistance [32,37,38]. Since heat stress can lead to alterations in centrosomes and different abnormal biological routes, such as mitotic slippage, cytokinesis failure, or cell fusion, it can be directly observed and responsible for the formation of polyploid cells after heat stress treatment.…”

Section: Introductionmentioning

confidence: 99%

Heat Stress-Induced Multiple Multipolar Divisions of Human Cancer Cells

Chen

Liu

Huang

et al. 2019

Cells

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Multipolar divisions of heated cells has long been thought to stem from centrosome aberrations of cells directly caused by heat stress. In this paper, through long-term live-cell imaging, we provide direct cellular evidences to demonstrate that heat stress can promote multiple multipolar divisions of MGC-803 and MCF-7 cells. Our results show that, besides facilitating centrosome aberration, polyploidy induced by heat stress is another mechanism that causes multipolar cell divisions, in which polyploid cancer cells engendered by mitotic slippage, cytokinesis failure, and cell fusion. Furthermore, we also find that the fates of theses polyploid cells depend on their origins, in the sense that the polyploid cells generated by mitotic slippage experience bipolar divisions with a higher rate than multipolar divisions, while those polyploid cells induced by both cytokinesis failure and cell fusion have a higher frequency of multipolar divisions compared with bipolar divisions. This work indicates that heat stress-induced multiple multipolar divisions of cancer cells usually produce aneuploid daughter cells, and might lead to genetically unstable cancer cells and facilitate tumor heterogeneity.

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Environmental stresses induce karyotypic instability in colorectal cancer cells

Cited by 24 publications

References 79 publications

Karyotype Aberrations in Action: The Evolution of Cancer Genomes and the Tumor Microenvironment

Karyotype Aberrations in Action: The Evolution of Cancer Genomes and the Tumor Microenvironment

Whole-genome duplication shapes the aneuploidy landscape of human cancers

Heat Stress-Induced Multiple Multipolar Divisions of Human Cancer Cells

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