scholarly journals Cell transformation disrupts the efficiency of chromosome segregation through microtubule detyrosination

2018 ◽  
Author(s):  
Virginia Silió ◽  
Jonathan B. Millar ◽  
Andrew D. McAinsh
Keyword(s):  
Chromosome Segregation ◽  
Epithelial To Mesenchymal Transition ◽  
Cell Transformation ◽  
Retinal Pigment ◽  
Mesenchymal Cell ◽  
Cell Types ◽  
Retinal Pigment Epithelial Cells ◽  
Mesenchymal Transition ◽  
Carboxypeptidase Inhibitor ◽  
Different Cell Types

The general principles of chromosome segregation are highly conserved throughout eukaryotic evolution. However, it is unknown whether there are differences in spindle or kinetochore composition or architecture which influence the efficiency chromosome segregation in different cell types. Here we show that the transition of human retinal pigment epithelial cells to a mesenchymal phenotype causes a stabilisation of kinetochore-microtubule attachments and an increase in the frequency of chromosome mis-segregation, due to inefficient error-correction, during mitosis. We find that this is caused by microtubule detyrosination during the epithelial-to-mesenchymal transition and that parthenolide, a tubulin carboxypeptidase inhibitor, efficiently reverts mes-enchymal cells to the epithelial mode of chromosome segregation. We propose that reprogramming the post-translational modifications of the mitotic spindle decreases mitotic fidelity and may contribute to CIN in mesenchymal cell populations during tumorigenesis.

scholarly journals MicroRNAs and Stem-like Properties: The Complex Regulation Underlying Stemness Maintenance and Cancer Development

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1074
Author(s):  
Giuseppina Divisato ◽  
Silvia Piscitelli ◽  
Mariantonietta Elia ◽  
Emanuela Cascone ◽  
Silvia Parisi
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Embryonic Stem ◽  
Cell Types ◽  
Cancer Development ◽  
Special Focus ◽  
Self Renewal ◽  
Mesenchymal Transition ◽  
Different Cell Types

Embryonic stem cells (ESCs) have the extraordinary properties to indefinitely proliferate and self-renew in culture to produce different cell progeny through differentiation. This latter process recapitulates embryonic development and requires rounds of the epithelial–mesenchymal transition (EMT). EMT is characterized by the loss of the epithelial features and the acquisition of the typical phenotype of the mesenchymal cells. In pathological conditions, EMT can confer stemness or stem-like phenotypes, playing a role in the tumorigenic process. Cancer stem cells (CSCs) represent a subpopulation, found in the tumor tissues, with stem-like properties such as uncontrolled proliferation, self-renewal, and ability to differentiate into different cell types. ESCs and CSCs share numerous features (pluripotency, self-renewal, expression of stemness genes, and acquisition of epithelial–mesenchymal features), and most of them are under the control of microRNAs (miRNAs). These small molecules have relevant roles during both embryogenesis and cancer development. The aim of this review was to recapitulate molecular mechanisms shared by ESCs and CSCs, with a special focus on the recently identified classes of microRNAs (noncanonical miRNAs, mirtrons, isomiRs, and competitive endogenous miRNAs) and their complex functions during embryogenesis and cancer development.

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