The telomere complex and the origin of the cancer stem cell
Author: A Torres-Montaner1,2
Affiliation:
1 Department of Pathology, Queen's Hospital, Rom Valley Way, London, Romford, RM7 OAG, UK. atorresmontaner@gmail.com.
2 Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de Cádiz, 11510 Puerto Real, Cádiz, Spain. atorresmontaner@gmail.com.
Conference/Journal: Biomark Res
Date published: 2021 Nov 4
Other:
Volume ID: 9 , Issue ID: 1 , Pages: 81 , Special Notes: doi: 10.1186/s40364-021-00339-z. , Word Count: 183
Exquisite regulation of telomere length is essential for the preservation of the lifetime function and self-renewal of stem cells. However, multiple oncogenic pathways converge on induction of telomere attrition or telomerase overexpression and these events can by themselves trigger malignant transformation. Activation of NFκB, the outcome of telomere complex damage, is present in leukemia stem cells but absent in normal stem cells and can activate DOT1L which has been linked to MLL-fusion leukemias. Tumors that arise from cells of early and late developmental stages appear to follow two different oncogenic routes in which the role of telomere and telomerase signaling might be differentially involved. In contrast, direct malignant transformation of stem cells appears to be extremely rare. This suggests an inherent resistance of stem cells to cancer transformation which could be linked to a stem cell'specific mechanism of telomere maintenance. However, tumor protection of normal stem cells could also be conferred by cell extrinsic mechanisms.
Keywords: Cell of cancer origin; EndoG; Hematopoietic stem cells; Senescence-associated secretoy phenotype (SASP); Telomere biology disorders; Telomere-associated secretoy phenotype (TASP).
PMID: 34736527 DOI: 10.1186/s40364-021-00339-z
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