TITLE:
Genomic Instability in Cancer I: DNA-Repair Triggering Primitive Hereditary 4n-Skewed, Amitotic Division-System, the Culprit in EMT/MET/Metaplasia Cancer-Concepts
AUTHORS:
Kirsten H. Walen
KEYWORDS:
Cancer Evolution, DNA-Damage-Repair, Mitotic Slippage, Hereditary Primitive Tetraploidy, 90° Amitotic Skewed Division, Fitness-Gain, Embryogenesis-Type EMT/MET, Human Cell Conservation
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.9 No.12,
December
13,
2018
ABSTRACT: The objective was to gain proof of genome damage-repair induced mitotic
slippage process (MSP) to 4n-diplochromosome skewed division-system, earlier
suggested to have “cancer-deciding” consequences. Our damage-model showed two
succeeding phases: molecular mutations for initiation of fitness-gained cells, and large
chromosomal changes to aneuploidy from inherited
DNA-breakage-repair inaccuracies. The mutations were gained while DNA-repair
and DNA-replication, co-existed in the route to tetraploidy, a phenomenon also expressed for
some existing unicellular organisms. These organisms also showed genome
reductive, amitotic, meioticlike division, and was the origin of human genome
conserved, self-inflicted 90° reorientation
of the 4n nucleus relative to the cytoskeleton axis. In the in vitro DNA-damage model, this
remarkable 4n-event deciding “flat-upright” cell-growth characteristics showed
several consequences, for example, cancer-important, E-cadherin-β-catenin cell-to-cell adherence
destruction, which gave diploid progeny cells, mobility freedom from cell contact inhibition, likely
in renewal tissues. This 4n-skewed division-system with inheritance in progeny
cells for repeat occurrences as mentioned for flat-up-right growth patterns is
similar to claimed concepts of metaplasia-EMT/MET
embryogenesis events in cancer evolution. A scrutiny of this literature, proof-wise invalidated
this embryological concept by tetraploid 8C cells occurring in MET events and, was
noted for small cell occurrence, i.e., diploidy
from 4n-8C reductive division, an also event for tumor relapse cells, derived
from genome damaging therapy agents. Pre-cancer
hyperplasia reported MSP, cadherincatenin destruction and 90° perpendicularity
to basal cell membrane. The DNA-damage-repair model can weed-out therapy-agents
triggering 4n-skewed division. Cancer-control, beginning-information, is likely
from mutational identity of the 4n derived fitness-gained cells.