Soumili Chakraborty, Amity University, Kolkata
Stem cells undergo asymmetric cell division to give rise to two daughter cells:
- One daughter cell which is similar to that of the original stem cell,
- And the second daughter cell differentiates into a non-stem cell.
Stem cells are largely studied to understand the underlying mechanisms, by which they contribute to the repair of damaged tissues and organs. But sometimes these same stem cells, turn out to be not so helpful. That’s because of a potential threat which they carry, which is of them becoming the very source of some of the most dreadful diseases, like Cancers!
The asymmetric cell division depicted by the normal stem cells of our bodies helps in executing the normal cell cycle process. Disruption of this asymmetric cell division often leads to an abnormal self-renewal and decrease in differentiation, and could therefore lead to the early onset of a tumorigenic transformation of stem and progenitor cells.
In neoplastic diseases, disruption in signalling networks associated with asymmetric division is observed. These typically give rise to a proliferative state, thereby causing an accumulation of stem-like cells with limited capacity to differentiate.
Mechanisms regulating asymmetric cell division have been studied in models ranging from Caenorhabditis elegans to mammals, with most studies being conducted on Drosophila. The Drosophila larval brain neuroblast is used as a novel model for the study of stem cell tumorigenesis.
At first, the brain tissue of the species undergoes massive overgrowth upon transplantation, killing the host within weeks. The implanted cells resemble many of the hallmarks of malignant neoplastic growth. They appear to be immortal and can be re-transplanted into successive hosts over the years. These transplanted cells often exhibit metastatic behaviour, by establishing secondary colonies in distant regions of the body.
In C. elegans, a series of asymmetric cell divisions in the early embryo are necessary for setting up the anterior/posterior, dorsal/ventral, and left/right axes of the body plan. In the past 30 years, the embryo of the nematode Caenorhabditis elegans has been used as a very powerful model to study the molecular and cellular basis of asymmetric cell division. Understanding this process in C. elegans may help us to have a better understanding of stem cell function and tumorigenesis in humans.
Cell cycle genes can regulate the asymmetric division and act as tumour suppressors. The manifestation of mutations in several such genes that are responsible for the regulation of the cell cycle influence asymmetric protein localization, specification the fates of distinct daughter cells, and the decision to undergo self-renewal or to differentiate.
Aurora-A and Polo kinases act as tumour suppressors by preventing excess self-renewal- The activation of cell cycle proteins, including CDK1, aurora A, and Polo, at prometaphase and metaphase, leads to a delicate temporal control of the asymmetric division.
There are numerous examples of human cancers that harbour alterations in orthologs of Drosophila genes related to asymmetric cell division. Many cancers are caused due to disrupted asymmetric cell division which may be caused by the disturbances in mechanisms. Further understanding of stem cell division in cancer is deemed necessary to provide opportunities for the development of better diagnostic and therapies for cancer.
Also read: Study reveals SARS-CoV-2 prevents the formation of new red blood cells
Sources:
Subhas Mukherjee, Jung Kong, Daniel J. Brat; Cancer stem cell division: when the rules of asymmetry are broken; 2014 Nov. 8; stem cells and development; DOI: 10.1089/scd.2014.0442
William Chia, W.Gregory Somers, Hongyan Wang; Drosophila neuroblast asymmetric division: cell cycle regulators, asymmetric protein localization and tumorogenesis; 2008, Jan 28; Journal of cell biology; DOI: 10.1083/jcb.200708159
Vincent Hyene, Nicolas T Chartier, Jean Claude Labbe; Understanding the role of Asymmetrical Cell Division in Cancer using C. elegans; May 2010; DOI: 10.1002/dvdy.22237
Morrison, S. J.; Kimble, J. (2006). “Asymmetric and symmetric stem-cell divisions in development and
Cancer”. Nature. 441 (7097): 1068–74. doi: 10.1038/nature04956. PMID 16810241.
Gönczy, P. and Rose, L.S. Asymmetric cell division and axis formation in the embryo (October 15, 2005), WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.30.1
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Truly informative article😊
excellent job, keep going😀😀