Version 1
: Received: 22 August 2023 / Approved: 23 August 2023 / Online: 24 August 2023 (09:43:20 CEST)
Version 2
: Received: 24 December 2023 / Approved: 25 December 2023 / Online: 26 December 2023 (09:54:12 CET)
How to cite:
Niculescu, V.F. Understanding Cancer from an Evolutionary Perspective; DSCD Cells as Cell-of-Origin in Non-Mutational Sporadic Cancers. Preprints2023, 2023081688. https://doi.org/10.20944/preprints202308.1688.v1
Niculescu, V.F. Understanding Cancer from an Evolutionary Perspective; DSCD Cells as Cell-of-Origin in Non-Mutational Sporadic Cancers. Preprints 2023, 2023081688. https://doi.org/10.20944/preprints202308.1688.v1
Niculescu, V.F. Understanding Cancer from an Evolutionary Perspective; DSCD Cells as Cell-of-Origin in Non-Mutational Sporadic Cancers. Preprints2023, 2023081688. https://doi.org/10.20944/preprints202308.1688.v1
APA Style
Niculescu, V.F. (2023). Understanding Cancer from an Evolutionary Perspective; DSCD Cells as Cell-of-Origin in Non-Mutational Sporadic Cancers. Preprints. https://doi.org/10.20944/preprints202308.1688.v1
Chicago/Turabian Style
Niculescu, V.F. 2023 "Understanding Cancer from an Evolutionary Perspective; DSCD Cells as Cell-of-Origin in Non-Mutational Sporadic Cancers" Preprints. https://doi.org/10.20944/preprints202308.1688.v1
Abstract
The life cycle of cancer follows the life cycle of the common ancestor of amoebozoans, metazoans, and fungi (AMF) and its systemic germline, which serves as a blueprint for all germlines capable of asymmetric cell division (ACD) and stem cell differentiation. Consequently, the oxygen sensitivity of the ancient non-gametogenic germline (Urgermline) was inherited by all germ and stem cell lines including the cancer germline. They all respond to Ugermline’s hyperoxia with loss of stemness and ACD ability and a dysregulated phenotype with irreparable DNA defects and defective symmetric cell divisions (DSCD). In protists, defective DSCD cells undergo an ancient MGRS repair program involving cell and nuclear fusion and hyperploid giant nuclei that restores the damaged genome to its former pre-DSCD state, with ACD potential and stemness. Human and metazoan DSCD use the same MGRS repair program inherited from the AMF ancestor. Ectopic DSCDs and DSCD-like phenotypes can survive in humans for many years in suitable niches. Under favorable environmental conditions, they also have access to the ancient MGRS repair mechanism including the ancient gene regulatory network (aGRN) and all other AMF genes. The aGRN takes control of cancer’s hybrid genome and represses human genes. It installs a G+S cancer life cycle of AMF imprinting that shapes the differentiation of naïve cancer stem cells (CSCs). CSCs are deeply homologous to the aGSCs of the AMF ancestor. Reprogramming of the DSCD genome by MGRS paves the way for oncogenesis. In this light, cancer is not a mutational or genetic disease, but a non-mutational genome-altering disease.
Keywords
cancer; asymmetric and symmetric cell cycling (ACD, SCD); loss of function; DNA-damaged cells; genomic repair; reprogramming; oncogenesis
Subject
Biology and Life Sciences, Cell and Developmental Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
