Attenuated Chromosome Oscillation as a Cause of Chromosomal Instability in Cancer Cells

Iemura, Kenji; Yoshizaki, Yujiro; Kuniyasu, Kinue; Tanaka, Kozo

doi:10.3390/cancers13184531

Cited by 5 publications

(2 citation statements)

References 210 publications

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“…Kinetochores that become stably aligned maintain their position within the metaphase plate by moving in an oscillatory manner around the equatorial plane [39,40]. The main mechanisms that maintain chromosome alignment in vertebrate cells include the regulation of k-fiber plus end dynamics by motors such as Kif18a/kinesin-8, sliding of bridging MTs, and the action of polar ejection forces (PEFs) [41][42][43][44][45][46], though the level of contribution of each mechanism is still unclear.…”

Section: Oscillating At the Equator-maintenance Of Alignmentmentioning

confidence: 99%

Polar Chromosomes—Challenges of a Risky Path

Vukušić

Tolić

2022

Cells

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The process of chromosome congression and alignment is at the core of mitotic fidelity. In this review, we discuss distinct spatial routes that the chromosomes take to align during prometaphase, which are characterized by distinct biomolecular requirements. Peripheral polar chromosomes are an intriguing case as their alignment depends on the activity of kinetochore motors, polar ejection forces, and a transition from lateral to end-on attachments to microtubules, all of which can result in the delayed alignment of these chromosomes. Due to their undesirable position close to and often behind the spindle pole, these chromosomes may be particularly prone to the formation of erroneous kinetochore-microtubule interactions, such as merotelic attachments. To prevent such errors, the cell employs intricate mechanisms to preposition the spindle poles with respect to chromosomes, ensure the formation of end-on attachments in restricted spindle regions, repair faulty attachments by error correction mechanisms, and delay segregation by the spindle assembly checkpoint. Despite this protective machinery, there are several ways in which polar chromosomes can fail in alignment, mis-segregate, and lead to aneuploidy. In agreement with this, polar chromosomes are present in certain tumors and may even be involved in the process of tumorigenesis.

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Section: Oscillating At the Equator-maintenance Of Alignmentmentioning

confidence: 99%

Polar Chromosomes—Challenges of a Risky Path

Vukušić

Tolić

2022

Cells

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“…Numerical CIN, hence, does not alter the nucleotide sequence in any chromosome, but only the number of copies of chromosomes, resulting in a state of aneuploidy. Numerical CIN emerges mostly from segregation errors during mitosis, with the underlying causes including mitotic checkpoint defects, centrosome amplification and chromosome oscillation [ 37 , 38 , 39 ]. Perhaps the most striking event that induces CIN is polyploidization or genome doubling, caused by cell fusion, endoreplication, or histone stress [ 40 , 41 ].…”

Section: Numerical and Structural Cin Generates New Karyotypesmentioning

confidence: 99%

Chromosomal Instability, Selection and Competition: Factors That Shape the Level of Karyotype Intra-Tumor Heterogeneity

Bosch

Derks

Miedema

2022

Cancers

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Intra-tumor heterogeneity (ITH) is a pan-cancer predictor of survival, with high ITH being correlated to a dismal prognosis. The level of ITH is, hence, a clinically relevant characteristic of a malignancy. ITH of karyotypes is driven by chromosomal instability (CIN). However, not all new karyotypes generated by CIN are viable or competitive, which limits the amount of ITH. Here, we review the cellular processes and ecological properties that determine karyotype ITH. We propose a framework to understand karyotype ITH, in which cells with new karyotypes emerge through CIN, are selected by cell intrinsic and cell extrinsic selective pressures, and propagate through a cancer in competition with other malignant cells. We further discuss how CIN modulates the cell phenotype and immune microenvironment, and the implications this has for the subsequent selection of karyotypes. Together, we aim to provide a comprehensive overview of the biological processes that shape the level of karyotype heterogeneity.

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ImmunoCellCycle-ID: A high-precision immunofluorescence-based method for cell cycle identification

Chen,

Suzuki

2024

Preprint

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The cell cycle is a fundamental process essential for cell proliferation, differentiation, and development. It consists of four major phases: G1, S, G2, and M. These phases collectively drive the reproductive cycle and are meticulously regulated by various proteins that play critical roles in both the prevention and progression of cancer. Traditional methods for studying these functions, such as flow cytometry, require a substantial number of cells to ensure accuracy. In this study, we have developed a user-friendly, immunofluorescence-based method for identifying cell cycle stages, providing single-cell resolution and precise identification of G1, early S, late S, early G2, late G2, and each sub-stage of the M phase using fluorescence microscopy. This method provides high-precision cell cycle identification and can serve as an alternative to, or in combination with, traditional flow cytometry to dissect detailed substages of the cell cycle in a variety of cell lines.

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Attenuated Chromosome Oscillation as a Cause of Chromosomal Instability in Cancer Cells

Cited by 5 publications

References 210 publications

Polar Chromosomes—Challenges of a Risky Path

Polar Chromosomes—Challenges of a Risky Path

Chromosomal Instability, Selection and Competition: Factors That Shape the Level of Karyotype Intra-Tumor Heterogeneity

ImmunoCellCycle-ID: A high-precision immunofluorescence-based method for cell cycle identification

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