Neural stemness unifies cell tumorigenicity and pluripotent differentiation potential

Zhang, Min; Liu, Yang; Shi, Lihua; Fang, Lei; Xu, Liyang; Cao, Ying

doi:10.1016/j.jbc.2022.102106

Cited by 11 publications

(45 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cancer cells at later stage of cancer progression are more dissimilar to the cells of cancer origin and show stronger tumorigenicity. Neural stemness and differentiation potential in cancer cells grow progressively with the progression of cancer, a rule that is confirmed by a serial xenotransplantation assay of cancer cells (Zhang et al, 2022). Although cancer cells share the regulatory networks and cell property with neural stem or embryonic neural cells, some essential disparities still exist, including extensive defects in genes (differentiation genes in particular) and genome in cancer cells and the difference in the microenvironments with which cancer cells or embryonic neural cells communicate, leading to chaotic differentiation of cancer cells.…”

Section: Neural Induction and Tumorigenesismentioning

confidence: 73%

“…It was demonstrated recently that cell tumorigenicity and pluripotency are coupled properties unified by neural stemness. Synchronic enhancement of neural stemness, tumorigenicity and pluripotency is accompanied by increased level of proteins involved in translation, ribosome biogenesis and spliceosome assembly, etc., and accordingly, increased events of alternative splicing in cancer cells (Zhang et al, 2022). It can be concluded that cancer cells are characteristic of neural stemness, but not mesenchymal state, in both cell features and regulatory networks.…”

Section: The "Mesenchymal State" Shares Little Similarity With Cancer...mentioning

confidence: 97%

“…Neural precursor/progenitor cells, which are tumorigenic and are capable of teratoma formation in immunodeficient mice (Xu et al, 2021), were isolated from teratocarcinoma/teratoma (Hasgekar et al, 1996;Kim et al, 2019). Therefore, ECs are characteristic of neural stemness, tumorigenicity and pluripotent differentiation potential, which are coupled cell properties (Cao, 2022;Zhang et al, 2022). Like neural induction during embryonic development, teratocarcinomas/teratomas are the consequence of the progressive loss of original cell identity and gain of neural stemness, i.e., gain of tumorigenicity and pluripotency, in both germ and somatic cells.…”

Section: Neural Induction and Tumorigenesismentioning

confidence: 99%

“…Growing evidence has shown that cancer cells, or generally tumorigenic cells, are characteristic of NSCs. Like NSCs and ECs, cells from different cancer types are capable of neuronal differentiation in response to inhibition of endogenous cancer promoting factors, which have a specific or enriched expression in embryonic neural cells during vertebrate embryogenesis, and play essential roles in maintaining neural stemness in both cancer cells and NSCs (Chen et al, 2021;Lei et al, 2019;Lu et al, 2017;Zhang et al, 2017;Zhang et al, 2022). In general, most genes (if not all) that promote cancers or are upregulated in cancer cells are neural stemness genes or genes with enriched expression in embryonic neural cells during vertebrate embryogenesis.…”

Section: Neural Induction and Tumorigenesismentioning

confidence: 99%

“…In other words, it was not clear whether CSCs of different cancer types have the property of stem/progenitor cells of their respective tissues of cancer origin, or all CSCs might have a common property of stemness, or CSCs might be of "cancer-specific" nature that is not comparable to any known stem cell types. In fact, similar to ECs, common cancer cells are also pluripotent because xenograft tumors formed by cancer cells show expression of markers of tissue/cell types derived from all three germ layers, for example, SOX1-expressing cells representing cells with neural stemness and derived from ectoderm, ACTA2-expressing cells derived from mesoderm, and AFP-expressing cells derived from endoderm (Xu et al, 2021;Cao, 2022;Zhang et al, 2022). These cells can be widely detected in different cancer types.…”

Section: Neural Induction and Tumorigenesismentioning

confidence: 99%

See 4 more Smart Citations

Neural Induction: the General Principle for Embryogenesis and Tumorigenesis

Cao¹

2022

Preprint

Self Cite

View full text Add to dashboard Cite

Some concepts/hypotheses have been proposed to explain the general rules behind the complexity of tumorigenesis. Characterization of the property of cancer cells and neural stem cells indicates that neural stemness underlies tumorigenicity and pluripotency, leading to the proposal that 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. The principle of 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 assume the neural default fate and turn into neuroectodermal cells. These cells 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 conjoined twins. A similar principle underlies tumorigenesis. Increasing evidence has demonstrated that the core property of cancer cells is neural stemness. Therefore, cancer cells are cells with the loss of original cell identity and gain of neural stemness, and consequently tumorigenicity and pluripotency, due to various intra-/extracellular insults in postnatal animals. Unlike that pluripotent cells (embryonic pluripotent cells, neural stem cells and cancer cells) can differentiate and integrate into embryonic development, cancer cells are capable of self-renewal and differentiation, but cannot integrate into normal tissues in a 2 postnatal animal, ultimately leading to tumor formation. Neural induction and the unique property of neural stemness provide an inclusive explanation for embryogenesis, conjoined twin formation and tumorigenesis. Based on these findings, I discuss about some confusion in cancer research, e.g., epithelial-mesenchymal transition, and propose to distinguish the causality and associations, and the causal and supporting factors involved in tumorigenesis, and suggest revisiting the focus of cancer research. Integration of evidence from developmental and cancer biology indicates that neural stemness determines tumorigenicity and pluripotency, and neural induction drives embryogenesis in gastrulating embryos but a similar process drives tumorigenesis in a postnatal animal.

show abstract

Section: Neural Induction and Tumorigenesismentioning

confidence: 73%

Section: The "Mesenchymal State" Shares Little Similarity With Cancer...mentioning

confidence: 97%

Section: Neural Induction and Tumorigenesismentioning

confidence: 99%

Section: Neural Induction and Tumorigenesismentioning

confidence: 99%

Section: Neural Induction and Tumorigenesismentioning

confidence: 99%

See 3 more Smart Citations

Neural Induction: the General Principle for Embryogenesis and Tumorigenesis

Cao¹

2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Stem cells in central nervous system diseases: Promising therapeutic strategies

Ying,

Zhang,

Zhang

et al. 2023

Experimental Neurology

View full text Add to dashboard Cite

Promoter hypermethylation of neural-related genes is compatible with stemness in solid cancers

Idris

Coussement

Alves

et al. 2023

Epigenetics & Chromatin

View full text Add to dashboard Cite

Background DNA hypermethylation is an epigenetic feature that modulates gene expression, and its deregulation is observed in cancer. Previously, we identified a neural-related DNA hypermethylation fingerprint in colon cancer, where most of the top hypermethylated and downregulated genes have known functions in the nervous system. To evaluate the presence of this signature and its relevance to carcinogenesis in general, we considered 16 solid cancer types available in The Cancer Genome Atlas (TCGA). Results All tested cancers showed significant enrichment for neural-related genes amongst hypermethylated genes. This signature was already present in two premalignant tissue types and could not be explained by potential confounders such as bivalency status or tumor purity. Further characterization of the neural-related DNA hypermethylation signature in colon cancer showed particular enrichment for genes that are overexpressed during neural differentiation. Lastly, an analysis of upstream regulators identified RE1-Silencing Transcription factor (REST) as a potential mediator of this DNA methylation signature. Conclusion Our study confirms the presence of a neural-related DNA hypermethylation fingerprint in various cancers, of genes linked to neural differentiation, and points to REST as a possible regulator of this mechanism. We propose that this fingerprint indicates an involvement of DNA hypermethylation in the preservation of neural stemness in cancer cells.

show abstract

Neural stemness unifies cell tumorigenicity and pluripotent differentiation potential

Cited by 11 publications

References 70 publications

Neural Induction: the General Principle for Embryogenesis and Tumorigenesis

Neural Induction: the General Principle for Embryogenesis and Tumorigenesis

Stem cells in central nervous system diseases: Promising therapeutic strategies

Promoter hypermethylation of neural-related genes is compatible with stemness in solid cancers

Contact Info

Product

Resources

About