Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Neural is Fundamental: Neural Stemness as the Ground State of Cell Tumorigenicity and Differentiation Potential

Version 1 : Received: 4 December 2020 / Approved: 7 December 2020 / Online: 7 December 2020 (07:02:34 CET)

How to cite: Cao, Y. Neural is Fundamental: Neural Stemness as the Ground State of Cell Tumorigenicity and Differentiation Potential. Preprints 2020, 2020120122 (doi: 10.20944/preprints202012.0122.v1). Cao, Y. Neural is Fundamental: Neural Stemness as the Ground State of Cell Tumorigenicity and Differentiation Potential. Preprints 2020, 2020120122 (doi: 10.20944/preprints202012.0122.v1).

Abstract

Tumorigenesis is a complex biological phenomenon that includes extensive genetic and phenotypic heterogeneities and complicated regulatory mechanisms. In the recent few years, our studies demonstrate that tumor-initiating cells are similar to neural stem/progenitor cells in regulatory networks, tumorigenicity and pluripotent differentiation potential. In the review, I will make further discussion on these observations and propose a rule of cell biology by integrating these findings with evidence from developmental biology, tumor biology and evolution, which suggests that neural stemness underlies two coupled cell properties, tumorigenicity and pluripotent differentiation potential. Tumorigenicity and phenotypic heterogeneity in tumor is a result of acquirement of neural stemness in cells. The neural stemness property of tumor-initiating cells can hopefully integrate different concepts/hypotheses underlying tumorigenesis. Neural stem cells/neural progenitors and tumor-initiating cells share regulatory networks; both exhibit neural stemness, tumorigenicity and differentiation potential; both are dependent on expression or activation of ancestral genes (the atavistic effect); both rely primarily on aerobic glycolytic metabolism; both can differentiate into various cells or tissues that are derived from three germ layers, resembling severely disorganized or more severely degenerated process of embryonic development; both are enriched in long genes with more splice variants that provide more plastic scaffolds for cell differentiation, etc. The property of neural stemness might be a key point to understand tumorigenesis and pluripotent differentiation potential, and possibly explain certain pathological observations in tumors that have been inexplicable. Therefore, behind the complexity of tumorigenesis might be a general rule of cell biology, i.e., neural stemness represents the ground state of cell tumorigenicity and pluripotent differentiation potential.

Subject Areas

neural stemness; neural stem/progenitor cell; tumor-initiating cell; neural ground state; neural default model; differentiation potential; tumorigenicity; tumorigenesis; evo-devo

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