Version 1
: Received: 18 March 2024 / Approved: 19 March 2024 / Online: 20 March 2024 (12:28:51 CET)
Version 2
: Received: 17 April 2024 / Approved: 17 April 2024 / Online: 18 April 2024 (08:06:19 CEST)
Version 3
: Received: 15 June 2024 / Approved: 17 June 2024 / Online: 17 June 2024 (07:57:12 CEST)
How to cite:
Niculescu, V. Re-evaluation of the Concept of Cancer Stem Cells and Cancer Stemness in the Light of Evolutionary Cancer Cell Biology (ECCB). Preprints2024, 2024031158. https://doi.org/10.20944/preprints202403.1158.v3
Niculescu, V. Re-evaluation of the Concept of Cancer Stem Cells and Cancer Stemness in the Light of Evolutionary Cancer Cell Biology (ECCB). Preprints 2024, 2024031158. https://doi.org/10.20944/preprints202403.1158.v3
Niculescu, V. Re-evaluation of the Concept of Cancer Stem Cells and Cancer Stemness in the Light of Evolutionary Cancer Cell Biology (ECCB). Preprints2024, 2024031158. https://doi.org/10.20944/preprints202403.1158.v3
APA Style
Niculescu, V. (2024). Re-evaluation of the Concept of Cancer Stem Cells and Cancer Stemness in the Light of Evolutionary Cancer Cell Biology (ECCB). Preprints. https://doi.org/10.20944/preprints202403.1158.v3
Chicago/Turabian Style
Niculescu, V. 2024 "Re-evaluation of the Concept of Cancer Stem Cells and Cancer Stemness in the Light of Evolutionary Cancer Cell Biology (ECCB)" Preprints. https://doi.org/10.20944/preprints202403.1158.v3
Abstract
According to the ECCB, cancer represents the transition of a genomically damaged multicellular cell to a lower level of cell organization, controlled by the ancestral gene regulatory network (GRN) from the ancestral compartment of human and metazoan genomes. Cancer adopts ancient mechanisms and rules of the common ancestor, similar to those observed in parasitic amoebae. In cancer, the productive cell line generating CSCs is a non-gametogenic cancer germline. This germline proliferates through asymmetric cell division (ACD phenotype). CSCs lack proliferative capacity; they persist in hypoxic niches in a quiescent cell state or transition to an amplifying cell state that performs cyst-like polyploidization cycles, giving rise to precursors and CSCs capable of differentiation. Malignization arises from genomically dysfunctional tetraploid germline cells (DSCD phenotype) that proliferate in a precancerous stage through symmetric cell cycles. DSCD progeny undergo homotypic fusion, forming multinucleated genome repair syncytia (MGRS pathway) driving carcinogenesis. During tumorigenesis, metastasis, and recurrence, subsequent germline clones initiate a cascade of increasingly pathogenic CSCs through mechanisms such as heterotypic cell fusion, soma-to-germ transition, and polyploid giant cell structures (PGCCs). Irradiation and chemotherapies drive some of the very few surviving but dysfunctional CSCs through a PGCC repair pathway homologous to the MGRS pathway of carcinogenesis. The large number of PGCCs during metastasis and recurrence results from the perpetual germline cell damage and CSC poverty induced by oxygen levels above 6.0% O2 (germline hyperoxia).
Keywords
Cancer;Entamoeba; germline; asymmetric cell division; CSCs; loss of function; MGRS/PGCC
Subject
Medicine and Pharmacology, Oncology and Oncogenics
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.
