scholarly journals Structural Chromosome Instability: Types, Origins, Consequences, and Therapeutic Opportunities

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3056
Author(s):  
Sebastián Omar Siri ◽  
Julieta Martino ◽  
Vanesa Gottifredi
Keyword(s):  
Cancer Treatment ◽  
Cell Survival ◽  
Therapeutic Target ◽  
Chromosomal Instability ◽  
Structural Changes ◽  
Chromosome Instability ◽  
Chromosome Abnormalities ◽  
Cellular Mechanisms ◽  
Genomic Changes ◽  
Structural Chromosome

Chromosomal instability (CIN) refers to an increased rate of acquisition of numerical and structural changes in chromosomes and is considered an enabling characteristic of tumors. Given its role as a facilitator of genomic changes, CIN is increasingly being considered as a possible therapeutic target, raising the question of which variables may convert CIN into an ally instead of an enemy during cancer treatment. This review discusses the origins of structural chromosome abnormalities and the cellular mechanisms that prevent and resolve them, as well as how different CIN phenotypes relate to each other. We discuss the possible fates of cells containing structural CIN, focusing on how a few cell duplication cycles suffice to induce profound CIN-mediated genome alterations. Because such alterations can promote tumor adaptation to treatment, we discuss currently proposed strategies to either avoid CIN or enhance CIN to a level that is no longer compatible with cell survival.

scholarly journals DNA-Replikationsstress, Mitose und genomische Instabilität

BIOspektrum ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 10-13
Author(s):  
Alicia Konrath ◽  
Ann-Kathrin Schmidt ◽  
Holger Bastians
Keyword(s):  
Dna Replication ◽  
Tumor Progression ◽  
Chromosome Aberrations ◽  
Chromosomal Instability ◽  
Chromosome Instability ◽  
Replication Stress ◽  
Functional Link ◽  
Structural Chromosome ◽  
Genomische Instabilität

AbstractChromosomal instability (CIN) is a hallmark of cancer and contributes to tumorigenesis and tumor progression. While structural CIN (S-CIN) leads to structural chromosome aberrations, whole chromosome instability (W-CIN) is defined by perpetual gains or losses of chromosomes during mitosis causing aneuploidy. Mitotic defects, but also abnormal DNA replication (replication stress) can lead to W-CIN. However, the functional link between replication stress, mitosis and aneuploidy is little understood.

scholarly journals DNA Replication Stress and Chromosomal Instability: Dangerous Liaisons

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 642
Author(s):  
Therese Wilhelm ◽  
Maha Said ◽  
Valeria Naim
Keyword(s):  
Chromosome Aberrations ◽  
Chromosomal Instability ◽  
Current Knowledge ◽  
Precancerous Lesions ◽  
Chromosome Instability ◽  
Replication Stress ◽  
Cancer Therapies ◽  
Age Related ◽  
Structural Chromosome ◽  
Dna Replication Stress

Chromosomal instability (CIN) is associated with many human diseases, including neurodevelopmental or neurodegenerative conditions, age-related disorders and cancer, and is a key driver for disease initiation and progression. A major source of structural chromosome instability (s-CIN) leading to structural chromosome aberrations is “replication stress”, a condition in which stalled or slowly progressing replication forks interfere with timely and error-free completion of the S phase. On the other hand, mitotic errors that result in chromosome mis-segregation are the cause of numerical chromosome instability (n-CIN) and aneuploidy. In this review, we will discuss recent evidence showing that these two forms of chromosomal instability can be mechanistically interlinked. We first summarize how replication stress causes structural and numerical CIN, focusing on mechanisms such as mitotic rescue of replication stress (MRRS) and centriole disengagement, which prevent or contribute to specific types of structural chromosome aberrations and segregation errors. We describe the main outcomes of segregation errors and how micronucleation and aneuploidy can be the key stimuli promoting inflammation, senescence, or chromothripsis. At the end, we discuss how CIN can reduce cellular fitness and may behave as an anticancer barrier in noncancerous cells or precancerous lesions, whereas it fuels genomic instability in the context of cancer, and how our current knowledge may be exploited for developing cancer therapies.

scholarly journals The wages of CIN

2008 ◽  
Vol 180 (4) ◽  
pp. 661-663 ◽  
Author(s):  
Karen W. Yuen ◽  
Arshad Desai
Keyword(s):  
Cancer Cells ◽  
Solid Tumors ◽  
Chromosomal Instability ◽  
Chromosome Instability ◽  
Spindle Checkpoint ◽  
Human Cells ◽  
Normal Cells ◽  
Chromosome Missegregation ◽  
Cell Biol ◽  
The Relationship

Aneuploidy and chromosome instability (CIN) are hallmarks of the majority of solid tumors, but the relationship between them is not well understood. In this issue, Thompson and Compton (Thompson, S.L., and D.A. Compton. 2008. Examining the link between chromosomal instability and aneuploidy in human cells. J. Cell. Biol. 180:665–672) investigate the mechanism of CIN in cancer cells and find that CIN arises primarily from defective kinetochore–spindle attachments that evade detection by the spindle checkpoint and persist into anaphase. They also explore the consequences of artificially elevating chromosome missegregation in otherwise karyotypically normal cells. Their finding that induced aneuploidy is rapidly selected against suggests that the persistence of aneuploid cells in tumors requires not only chromosome missegregation but also additional, as yet poorly defined events.

A high frequency of structural chromosome abnormalities in a south central texas cytogenetics laboratory

1984 ◽  
Vol 19 (2) ◽  
pp. 347-358 ◽  
Author(s):  
Robert S. Young ◽  
Kathryn L. Hansen ◽  
Steven D. Shapiro ◽  
Ronald J. Jorgenson
Keyword(s):  
High Frequency ◽  
Chromosome Abnormalities ◽  
South Central ◽  
Structural Chromosome ◽  
Central Texas

scholarly journals The Role of Cellular Prion Protein in Cancer Biology: A Potential Therapeutic Target

2021 ◽  
Vol 11 ◽  
Author(s):  
Manqiu Ding ◽  
Yongqiang Chen ◽  
Yue Lang ◽  
Li Cui
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Cell Survival ◽  
Cancer Cells ◽  
Prion Protein ◽  
Therapeutic Target ◽  
Cancer Biology ◽  
Cellular Prion Protein ◽  
Potential Therapeutic Target

Prion protein has two isoforms including cellular prion protein (PrPC) and scrapie prion protein (PrPSc). PrPSc is the pathological aggregated form of prion protein and it plays an important role in neurodegenerative diseases. PrPC is a glycosylphosphatidylinositol (GPI)-anchored protein that can attach to a membrane. Its expression begins at embryogenesis and reaches the highest level in adulthood. PrPC is expressed in the neurons of the nervous system as well as other peripheral organs. Studies in recent years have disclosed the involvement of PrPC in various aspects of cancer biology. In this review, we provide an overview of the current understanding of the roles of PrPC in proliferation, cell survival, invasion/metastasis, and stem cells of cancer cells, as well as its role as a potential therapeutic target.

scholarly journals Could GLUT12 be a Potential Therapeutic Target in Cancer Treatment? A Preliminary Report

2015 ◽  
Vol 6 (2) ◽  
pp. 139-143 ◽  
Author(s):  
Jonai Pujol-Gimenez ◽  
Fátima Pérez de Heredia ◽  
Miguel Angel Idoate ◽  
Rachel Airley ◽  
María Pilar Lostao ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Therapeutic Target ◽  
Preliminary Report ◽  
Potential Therapeutic Target

Abstract 14309: A Novel Fibroblast Activation Inhibitor, NM922, Attenuates Maladaptive Fibrotic Remodeling to Preserve Cardiac Function Following the Onset of Heart Failure

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Jessica M Bradley ◽  
Craig M Ziblich ◽  
Kazi N Islam ◽  
Amanda M Rushing ◽  
David J Polhemus ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Structural Changes ◽  
Volume Fraction ◽  
Left Ventricular ◽  
Normal Fibroblast ◽  
Wall Thickening ◽  
Cellular Mechanisms ◽  
Collagen Formation ◽  
Failing Heart

Background: Cardiac fibroblasts are critical mediators of fibrotic remodeling in the failing heart. These maladaptive structural changes can worsen cardiac function accelerating the progression to decompensated heart failure (HF). We investigated the effects of a novel inhibitor of the conversion of normal fibroblast to the myofibroblast phenotype in the setting of pressure overload induced HF. Methods: Male C57BL/6J mice (10 wks) were subjected to transverse aortic constriction (TAC; 27 g needle) and NM922 (NovoMedix, LLC50 mg/kg/d i.p.) or VEH (DMSO + HS-15) was administered daily starting at 6 wks post TAC. Echocardiography was assessed at baseline and for 16 wks post TAC. At the 16 wk endpoint, mice were sacrificed and hearts were collected for biochemical and molecular assessment. Results: NM922 significantly attenuated TAC-induced left ventricular (LV) dilation at 16 wks post TAC (LVEDD: 3.5 ± 0.1 vs. 4.5 ± 0.2 mm, p < 0.01; LVESD: 2.5 ± 0.2 vs. 3.8 ± 0.3 mm, p < 0.01) compared to VEH. NM922 treated mice displayed reduced wall thickening (LVPWd: 1.0 ± 0.03 vs. 1.2 ± 0.05 mm; p < 0.05) at 10 wks post TAC compared to VEH. LV ejection fraction (LVEF) was preserved in NM922 treated mice at 8-16 wks post TAC compared to VEH (*p < 0.05; **p < 0.001) compared to VEH. Treatment with NM922 resulted in reductions in heart (8.5 ± 0.5 vs. 12.0 ± 0.9 mg/mm; p < 0.01) and lung (8.2 ± 0.3 vs. 11.5 ± 0.6 mg/mm; p < 0.0001) weights compared to VEH. Picrosirius Red staining revealed that NM922 reduced cardiac interstitial collagen volume fraction by 50% (p < 0.05 vs. VEH). Circulating BNP levels trended toward lower (p = 0.08) in the NM922 mice when compared to VEH. Conclusion: Chronic treatment with NM922 following the onset of cardiac hypertrophy and HF resulted in attenuated myocardial collagen formation and adverse remodeling with preservation of LVEF. Future studies are aimed at further elucidation of the molecular and cellular mechanisms by which this novel agent protects the failing heart.

Estrogen signaling: An emanating therapeutic target for breast cancer treatment

2019 ◽  
Vol 177 ◽  
pp. 116-143 ◽  
Author(s):  
Tanmay Saha ◽  
Subhajit Makar ◽  
Rayala Swetha ◽  
Gopichand Gutti ◽  
Sushil K. Singh
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Therapeutic Target ◽  
Breast Cancer Treatment ◽  
Estrogen Signaling
Sign in / Sign up

Export Citation Format

Share Document