Cancer as an Embryological Phenomenon and Its Developmental Pathways: A Hypothesis regarding the Contribution of the Noncanonical Wnt Pathway

Cofre, Jaime; Saalfeld, Kay; Abdelhay, Eliana

doi:10.1155/2019/4714781

Cited by 7 publications

(5 citation statements)

References 196 publications

(206 reference statements)

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“…Numerous previous studies, dating as far back as 1858 (Virchow's embryonal rest hypothesis), have observed parallels between cancer and development (55)(56)(57), proposing that cancer initiating cells are stuck at an earlier undifferentiated precursor developmental stage of the respective cell type, with activated immune suppressive and mesenchymal gene programs characteristic of early development (57). This would suggest that genes with perturbed expression in cancer are likely to be involved in tissue development and function.…”

Section: Discussionmentioning

confidence: 99%

Prioritizing and characterizing functionally relevant genes across human tissues

Somepalli

Sahoo

Singh

et al. 2021

Preprint

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Knowledge of genes that are critical to a tissue’s function remains difficult to ascertain and presents a major bottleneck toward a mechanistic understanding of genotype-phenotype links. Here, we present the first machine learning model – FUGUE – combining transcriptional and network features, to predict tissue-relevant genes across 30 human tissues. FUGUE achieves an average cross-validation auROC of 0.86 and auPRC of 0.50 (expected 0.09). In three independent datasets, FUGUE accurately distinguishes tissue or cell type-specific genes, significantly outperforming the conventional metric based on tissue-specific expression alone. Comparison of tissue-relevant transcription factors across tissue recapitulate their developmental relationships. Interestingly, the tissue-relevant genes cluster on the genome within topologically associated domains and furthermore, are highly enriched for differentially expressed genes in the corresponding cancer type. We provide the prioritized gene lists in 30 human tissues and an open-source software to prioritize genes in a novel context given multi-sample transcriptomic data.

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Section: Discussionmentioning

confidence: 99%

Prioritizing and characterizing functionally relevant genes across human tissues

Somepalli

Sahoo

Singh

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Numerous previous studies, dating as far back as 1858 (Virchow's embryonal rest hypothesis), have observed parallels between cancer and development [57][58][59], proposing that cancer initiating cells are stuck at an earlier undifferentiated precursor developmental stage of the respective cell type, with activated immune suppressive and mesenchymal gene programs characteristic of early development [59]. This would suggest that genes with perturbed expression in cancer are likely to be involved in tissue development and function.…”

Section: Discussionmentioning

confidence: 99%

Prioritizing and characterizing functionally relevant genes across human tissues

et al. 2021

View full text Add to dashboard Cite

Knowledge of genes that are critical to a tissue’s function remains difficult to ascertain and presents a major bottleneck toward a mechanistic understanding of genotype-phenotype links. Here, we present the first machine learning model–FUGUE–combining transcriptional and network features, to predict tissue-relevant genes across 30 human tissues. FUGUE achieves an average cross-validation auROC of 0.86 and auPRC of 0.50 (expected 0.09). In independent datasets, FUGUE accurately distinguishes tissue or cell type-specific genes, significantly outperforming the conventional metric based on tissue-specific expression alone. Comparison of tissue-relevant transcription factors across tissue recapitulate their developmental relationships. Interestingly, the tissue-relevant genes cluster on the genome within topologically associated domains and furthermore, are highly enriched for differentially expressed genes in the corresponding cancer type. We provide the prioritized gene lists in 30 human tissues and an open-source software to prioritize genes in a novel context given multi-sample transcriptomic data.

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“…The zinc-finger transcription factors GATA4, which play important roles in BC progression from an early stage, and GATA6, which is overexpressed in BC and promotes BC cell epithelial-mesenchymal transition (EMT) [64] are essential for embryonic development during gastrulation [65]. Cofre et al (2019) showed that both developmental pathways in gastrulation and cancer require the ability to respond to environmental stimuli [66]. Thus, the Wnt signaling pathway has been reported to be highly conserved in metazoan animals and to play a critical role in controlling embryo and organ development, as well as in BC cells transformation, where its alterations have been correlated with mutations, amplifications, deletions, DNA methylation, and post-translational modification of proteins (PTMs) [67].…”

Section: Bc Is a Developmental Disordermentioning

confidence: 99%

Onco-Breastomics: An Eco-Evo-Devo Holistic Approach

Neagu,

Whitham,

Bruno

et al. 2024

IJMS

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Known as a diverse collection of neoplastic diseases, breast cancer (BC) can be hyperbolically characterized as a dynamic pseudo-organ, a living organism able to build a complex, open, hierarchically organized, self-sustainable, and self-renewable tumor system, a population, a species, a local community, a biocenosis, or an evolving dynamical ecosystem (i.e., immune or metabolic ecosystem) that emphasizes both developmental continuity and spatio-temporal change. Moreover, a cancer cell community, also known as an oncobiota, has been described as non-sexually reproducing species, as well as a migratory or invasive species that expresses intelligent behavior, or an endangered or parasite species that fights to survive, to optimize its features inside the host’s ecosystem, or that is able to exploit or to disrupt its host circadian cycle for improving the own proliferation and spreading. BC tumorigenesis has also been compared with the early embryo and placenta development that may suggest new strategies for research and therapy. Furthermore, BC has also been characterized as an environmental disease or as an ecological disorder. Many mechanisms of cancer progression have been explained by principles of ecology, developmental biology, and evolutionary paradigms. Many authors have discussed ecological, developmental, and evolutionary strategies for more successful anti-cancer therapies, or for understanding the ecological, developmental, and evolutionary bases of BC exploitable vulnerabilities. Herein, we used the integrated framework of three well known ecological theories: the Bronfenbrenner’s theory of human development, the Vannote’s River Continuum Concept (RCC), and the Ecological Evolutionary Developmental Biology (Eco-Evo-Devo) theory, to explain and understand several eco-evo-devo-based principles that govern BC progression. Multi-omics fields, taken together as onco-breastomics, offer better opportunities to integrate, analyze, and interpret large amounts of complex heterogeneous data, such as various and big-omics data obtained by multiple investigative modalities, for understanding the eco-evo-devo-based principles that drive BC progression and treatment. These integrative eco-evo-devo theories can help clinicians better diagnose and treat BC, for example, by using non-invasive biomarkers in liquid-biopsies that have emerged from integrated omics-based data that accurately reflect the biomolecular landscape of the primary tumor in order to avoid mutilating preventive surgery, like bilateral mastectomy. From the perspective of preventive, personalized, and participatory medicine, these hypotheses may help patients to think about this disease as a process governed by natural rules, to understand the possible causes of the disease, and to gain control on their own health.

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Cancer as an Embryological Phenomenon and Its Developmental Pathways: A Hypothesis regarding the Contribution of the Noncanonical Wnt Pathway

Cited by 7 publications

References 196 publications

Prioritizing and characterizing functionally relevant genes across human tissues

Prioritizing and characterizing functionally relevant genes across human tissues

Prioritizing and characterizing functionally relevant genes across human tissues

Onco-Breastomics: An Eco-Evo-Devo Holistic Approach

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