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

Cao, Ying

doi:10.1007/s12015-021-10275-y

Cited by 10 publications

(36 citation statements)

References 221 publications

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“…neural, may be a key feature of tumorigenesis, which is hypothesized to represent the culmination of a process of gradual loss of a cell's original identity and gain of the properties of NSC/Neural Progenitor Cells. [33][34][35] The changes of cell state, e.g. to LumHR-major or to LumSec-HLA, the latter characterized by the expression of the chemokine ligand 20 (CCL20) 19 , has been noted to be involved in breast cancer progression, EMT, migration and invasion.…”

Section: Subsequent Analysis Of Histone Acetylation and Methylation U...mentioning

confidence: 99%

_Metabolicshift to serine pathway induced by lipids confers oncogenic properties in non-transformed breast cells

Eduardo,

Cottone,

McCloskey

et al. 2024

Preprint

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A lipid metabolism gene signature is associated with the risk of estrogen negative breast cancer (ER-BC). In vitro, lipid exposure alters histone methylation affecting gene expression and increasing flux through various metabolic reactions; but little is known about the mechanism(s) linking lipids and epigenetic reprogramming with the genesis of ER-BC. Here we show that the metabolism of the medium-chain fatty acid Octanoic Acid (OA) in preference to glucose and glutamine results in a metabolic shift toward the serine pathway increasing the production of SAM, glutathione, and 2-HG, with implications for oncogenesis: SAM production results in epigenetic fostered plasticity leading to reprogramming/selecting cells that express Neural, EMT and BC related genes. 2-HG exposure results in appearance of DNA breaks, potentially consequent to the inhibition of essential demethylases for HR repair. ROS increases shortly after OA exposure and is mitigated by antioxidant defenses, which favors/enables the survival of specific cell subtypes.

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Section: Subsequent Analysis Of Histone Acetylation and Methylation U...mentioning

confidence: 99%

_Metabolicshift to serine pathway induced by lipids confers oncogenic properties in non-transformed breast cells

Eduardo,

Cottone,

McCloskey

et al. 2024

Preprint

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“…These results suggest the critical importance of embryonic neural genes and neural precursor cells in tissue differentiation. Neural stemness, refering to the collective property of primitive neural stem cells (NSCs), neural crest cells and adult NSCs, represents the general stemness, defining tumorigenicity and pluripotent differentiation potential, a notion that has been experimentally clarified ( Clarke et al, 2000 ; Tropepe et al, 2001 ; Xu et al, 2021 ; Cao, 2022 ; Zhang et al, 2022 ). This unique property of neural stemness might be predestined by the evolutionary advantage of neural regulatory networks ( Xu et al, 2021 ; Cao, 2022 ).…”

Section: Embryonic Neural Induction and Embryogenesismentioning

confidence: 99%

“…Ectopic neural induction during gastrulation causes formation of a conjoined twin. Neural stemness is characterized as the essential property of tumorigenic and pluripotent cells, and tumorigenesis could be envisioned a progressive loss of original cell identity and gain of neural stemness in postnatal cells ( Southall et al, 2014 ; Cao, 2017 ; Li et al, 2020 ; Cao, 2022 ; Zhang et al, 2022 ), reflecting a neural induction-like effect. One obvious example for the comparability of tumorigenesis as a conjoined twin formation should be the teratocarcinomas/teratomas, which are composed of disorganized but histologically identifiable tissues or organs derived from all three germ layers, such as undifferentiated neural epithelial tissue and differentiated nerves from ectoderm, gut and glandular tissues from endoderm, and cartilaginous and muscle tissues from mesoderm.…”

Section: Neural Induction-like Process and Tumorigenesismentioning

confidence: 99%

“…Therefore, ECs are characteristic of neural stemness, tumorigenicity and pluripotent differentiation potential. Like neural induction during embryonic development, teratocarcinomas/teratomas are the consequence of progressive loss of original cell identity and gain of neural stemness, which contributes to tumorigenicity and pluripotency ( Xu et al, 2021 ; Cao, 2022 ; Zhang et al, 2022 ), in either germ or somatic cells.…”

Section: Neural Induction-like Process and Tumorigenesismentioning

confidence: 99%

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Neural induction drives body axis formation during embryogenesis, but a neural induction-like process drives tumorigenesis in postnatal animals

Cao

2023

Front. Cell Dev. Biol.

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Characterization of cancer cells and neural stem cells indicates that tumorigenicity and pluripotency are coupled cell properties determined by neural stemness, and tumorigenesis represents a process of progressive loss of original cell identity and gain of neural stemness. This reminds of a most fundamental process required for the development of the nervous system and body axis during embryogenesis, i.e., embryonic neural induction. Neural induction is that, in response to extracellular signals that are secreted by the Spemann-Mangold organizer in amphibians or the node in mammals and inhibit epidermal fate in ectoderm, the ectodermal cells lose their epidermal fate and assume the neural default fate and consequently, turn into neuroectodermal cells. They further differentiate into the nervous system and also some non-neural cells via interaction with adjacent tissues. Failure in neural induction leads to failure of embryogenesis, and ectopic neural induction due to ectopic organizer or node activity or activation of embryonic neural genes causes a formation of secondary body axis or a conjoined twin. During tumorigenesis, cells progressively lose their original cell identity and gain of neural stemness, and consequently, gain of tumorigenicity and pluripotency, due to various intra-/extracellular insults in cells of a postnatal animal. Tumorigenic cells can be induced to differentiation into normal cells and integrate into normal embryonic development within an embryo. However, they form tumors and cannot integrate into animal tissues/organs in a postnatal animal because of lack of embryonic inducing signals. Combination of studies of developmental and cancer biology indicates that neural induction drives embryogenesis in gastrulating embryos but a similar process drives tumorigenesis in a postnatal animal. Tumorigenicity is by nature the manifestation of aberrant occurrence of pluripotent state in a postnatal animal. Pluripotency and tumorigenicity are both but different manifestations of neural stemness in pre- and postnatal stages of animal life, respectively. Based on these findings, I discuss about some confusion in cancer research, propose to distinguish the causality and associations and discriminate causal and supporting factors involved in tumorigenesis, and suggest revisiting the focus of cancer research.

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“…It remains to be seen if Notch signaling activation is a universal requisite for stem cell niche formation, which seems to be the tendency to which the discoveries so far point. Similarly, the concept of stem cell niches and stem cells is ever evolving, and recent studies suggest a unifying neural stemness as the ground state of tumorigenicity ( Cao, 2022 ; Zhang et al, 2022 ). It draws significant parallels between tumorigenicity and pluripotent differentiation potential, both of which provide evidence for common cellular and biochemical processes (e.g., cell cycle, gene expression, and metabolism), which paints a picture of fundamental and universal mechanisms that govern the development of organisms.…”

Section: Stem Cell Niches For the Drosophila Germl...mentioning

confidence: 99%

Notch signaling sculpts the stem cell niche

Zamfirescu

Yatsenko

Shcherbata

2022

Front. Cell Dev. Biol.

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Adult stem cells depend on their niches for regulatory signaling that controls their maintenance, division, and their progeny differentiation. While communication between various types of stem cells and their niches is becoming clearer, the process of stem cell niche establishment is still not very well understood. Model genetic organisms provide simplified systems to address various complex questions, for example, how is a stem cell niche formed? What signaling cascades induce the stem cell niche formation? Are the mechanisms of stem cell niche formation conserved? Notch signaling is an evolutionarily conserved pathway first identified in fruit flies, crucial in fate acquisition and spatiotemporal patterning. While the core logic behind its activity is fairly simple and requires direct cell–cell interaction, it reaches an astonishing complexity and versatility by combining its different modes of action. Subtleties such as equivalency between communicating cells, their physical distance, receptor and ligand processing, and endocytosis can have an effect on the way the events unfold, and this review explores some important general mechanisms of action, later on focusing on its involvement in stem cell niche formation. First, looking at invertebrates, we will examine how Notch signaling induces the formation of germline stem cell niche in male and female Drosophila. In the developing testis, a group of somatic gonadal precursor cells receive Delta signals from the gut, activating Notch signaling and sealing their fate as niche cells even before larval hatching. Meanwhile, the ovarian germline stem cell niche is built later during late larval stages and requires a two-step process that involves terminal filament formation and cap cell specification. Intriguingly, double security mechanisms of Notch signaling activation coordinated by the soma or the germline control both steps to ensure the robustness of niche assembly. Second, in the vast domains of mammalian cellular signaling, there is an emerging picture of Notch being an active player in a variety of tissues in health and disease. Notch involvement has been shown in stem cell niche establishment in multiple organs, including the brain, muscle, and intestine, where the stem cell niches are essential for the maintenance of adult stem cells. But adult stem cells are not the only cells looking for a home. Cancer stem cells use Notch signaling at specific stages to gain an advantage over endogenous tissue and overpower it, at the same time acquiring migratory and invasive abilities to claim new tissues (e.g., bone) as their territory. Moreover, in vitro models such as organoids reveal similar Notch employment when it comes to the developing stem cell niches. Therefore, a better understanding of the processes regulating stem cell niche assembly is key for the fields of stem cell biology and regenerative medicines.

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

Cited by 10 publications

References 221 publications

_Metabolicshift to serine pathway induced by lipids confers oncogenic properties in non-transformed breast cells

_Metabolicshift to serine pathway induced by lipids confers oncogenic properties in non-transformed breast cells

Neural induction drives body axis formation during embryogenesis, but a neural induction-like process drives tumorigenesis in postnatal animals

Notch signaling sculpts the stem cell niche

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