Neurons generated from carcinoma stem cells support cancer progression

Lu, Ran; Fan, Cheng; Shangguan, Wenqi; Liu, Yuan; Liu, Yu; Ya-zhen, Shang; Yin, Dongqin; Zhang, Shengliang; Huang, Qiaorong; Li, Xue; Wei, Meng; Xu, Hong; Zhou, Zong‐Guang; Hu, Jian-Kun; Liu, Weimin; Liu, Lunxu; Mo, Xianming

doi:10.1038/sigtrans.2016.36

Cited by 93 publications

(97 citation statements)

References 33 publications

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“…Considering cancer heterogeneity, it might be that cells at different stages of a cancer type or of different cancer types express different subsets of neural genes. Besides our observation, a recent work also reported neuronal differentiation of gastric cancer stem cells (24). It is likely that among other chromatin modification enzymes with neural specific expression identified in the study, some should also regulate neuronal differentiation in cancer cells.…”

Section: Cancer Cells Can Be Terminally Differentiatedsupporting

confidence: 83%

“…Numerous studies have reported the importance of neural development signals during cancer development and progression, including those listed in supplemental Tables S4 -S6. Many cancer types, such as gastric and colon cancer, show neurogenesis and increases in nerve density (24,46,47), and denervation suppresses cancer (47). Benign prostatic basal cells that are enriched for stem cell and neural/neuronal genes are associated with more aggressive potential (48).…”

Section: Cancer Cells Share a Regulatory Network With Embryonic Neuramentioning

confidence: 99%

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Similarity in gene-regulatory networks suggests that cancer cells share characteristics of embryonic neural cells

Zhang

Lei

et al. 2017

Journal of Biological Chemistry

127

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Cancer cells are immature cells resulting from cellular reprogramming by gene misregulation, and redifferentiation is expected to reduce malignancy. It is unclear, however, whether cancer cells can undergo terminal differentiation. Here, we show that inhibition of the epigenetic modification enzyme enhancer of zeste homolog 2 (EZH2), histone deacetylases 1 and 3 (HDAC1 and -3), lysine demethylase 1A (LSD1), or DNA methyltransferase 1 (DNMT1), which all promote cancer development and progression, leads to postmitotic neuron-like differentiation with loss of malignant features in distinct solid cancer cell lines. The regulatory effect of these enzymes in neuronal differentiation resided in their intrinsic activity in embryonic neural precursor/progenitor cells. We further found that a major part of pan-cancer-promoting genes and the signal transducers of the pan-cancer-promoting signaling pathways, including the epithelial-to-mesenchymal transition (EMT) mesenchymal marker genes, display neural specific expression during embryonic neurulation. In contrast, many tumor suppressor genes, including the EMT epithelial marker gene that encodes cadherin 1 (), exhibited non-neural or no expression. This correlation indicated that cancer cells and embryonic neural cells share a regulatory network, mediating both tumorigenesis and neural development. This observed similarity in regulatory mechanisms suggests that cancer cells might share characteristics of embryonic neural cells.

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Section: Cancer Cells Can Be Terminally Differentiatedsupporting

confidence: 83%

Section: Cancer Cells Share a Regulatory Network With Embryonic Neuramentioning

confidence: 99%

Similarity in gene-regulatory networks suggests that cancer cells share characteristics of embryonic neural cells

Zhang

Lei

et al. 2017

Journal of Biological Chemistry

127

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“…Besides, colorectal and gastric cancer stem cells show neuronal differentiation potential [9]. These studies suggest that neural genes and neural properties might play a cell-autonomous role, rather than a mere crosstalk, in promoting tumorigenesis.…”

Section: Introductionmentioning

confidence: 89%

Neural stemness contributes to cell tumorigenicity

Zhang

Shi

et al. 2020

Preprint

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Background Previous studies demonstrated the dependence of cancer on nerve. Recently, a growing number of studies reveal that cancer cells share the property and regulatory network with neural stem/progenitor cells. However, relationship between the property of neural stemness and cell tumorigenicity is unknown. Results We show that neural stem/progenitor cells, but not non-neural embryonic or somatic stem/progenitor cell types, exhibit tumorigenicity and the potential for differentiation into tissue types of all germ layers when they are placed in non-native environment by transplantation into immunodeficient nude mice. Likewise, cancer cells capable of tumor initiation have the property of neural stemness because of their abilities in neurosphere formation in neural stem cell-specific serum-free medium and in differentiation potential, in addition to their neuronal differentiation potential that was characterized previously. Moreover, loss of a pro-differentiation factor in myoblasts, which have no tumorigenicity, lead to the loss of myoblast identity, and gain of the property of neural stemness, tumorigenicity and potential for re-differentiation. These suggest that the property of neural stemness contributes to cell tumorigenicity, and tumor phenotypic heterogeneity might be an effect of differentiation potential of neural stemness. Bioinformatic analysis reveals that neural genes in general are correlated with embryonic development and cancer, in addition to their role in neural development; whereas non-neural genes are not. Most of neural specific genes emerged in typical species representing transition from unicellularity to multicellularity during evolution. Genes in Monosiga brevicollis, a unicellular species that is a closest known relative of metazoans, are biased toward neural cells. Conclusions We suggest that the property of neural stemness is the source of cell tumorigenicity. This is due to that neural biased unicellular state is the ground state for multicellularity and hence cell type diversification or differentiation during evolution, and tumorigenesis is a process of restoration of neural ground state in somatic cells along a default route that is pre-determined by an evolutionary advantage of neural state.

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“…The lentiviral vector expressing red fluorescent protein (RFP) under (EF) human elongation factor‐1 alpha promoter and the corresponding viruses were from Genepharma (Shanghai, China). CoCSC infection was performed as previously described …”

Section: Methodsmentioning

confidence: 99%

“…CoCSC infection was performed as previously described. (24) In vivo xenotransplantation of cancer cells. Studies involving nude mice were approved by the Sichuan University Institutional Animal Care and Use Committee.…”

Section: Methodsmentioning

confidence: 99%

Endothelium originated from colorectal cancer stem cells constitute cancer blood vessels

et al. 2017

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Tumor growth depends on the formation of blood vessels that provide the supply of nutrients and oxygen. Previous data have shown that glioblastoma stem cells are able to give rise to vascular cells to constitute the functional vessels in tumor tissues. However, which kinds of vascular cells are generated from glioblastoma stem cells is largely debated. In addition, there is little evidence showing that the stem cells from other kinds of tumors can produce vascular cells to constitute the functional blood vessels in tumor tissues. Here we show that cancer stem cells of human colorectal carcinomas (CoCSC) can give rise to vascular endothelial cells and compose the vasculatures in cancer tissues. The human‐cell‐specific nuclear antigen NuMA + vascular endothelial cells were detected in the blood vessels in xenografts derived from CoCSC. NuMA + endothelial cells incorporated into functional blood vessels. Our data indicate that the cancer stem cells derived from human colorectal carcinomas have the capacity to generate functional blood vessels and provide a new mechanism for tumor vasculogenesis in carcinoma.

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Neurons generated from carcinoma stem cells support cancer progression

Cited by 93 publications

References 33 publications

Similarity in gene-regulatory networks suggests that cancer cells share characteristics of embryonic neural cells

Similarity in gene-regulatory networks suggests that cancer cells share characteristics of embryonic neural cells

Neural stemness contributes to cell tumorigenicity

Endothelium originated from colorectal cancer stem cells constitute cancer blood vessels

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