Gatekeeper transcription factors regulate switch between lineage preservation and cell plasticity

T, Ray; Shah, Anit; Ga, Bulla; Ps, Ray

doi:10.1101/2020.03.19.999433

Cited by 2 publications

(1 citation statement)

References 27 publications

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“…These cells account for the characteristic desmoplasia and dedifferentiation of the high-grade carcinomas 50,51 . The set of transcription factors that seem essential in the maintenance of these phenotypes are the Paired related homeobox 1 (Prrx 1), the paired-related homeobox protein SHOT (Shox2), the AP-1 Transcription Factor Subunit (c-fos), the Snail Family Transcriptional Repressor 2 (Slug), and the Twist family bHLH transcription factor 1 (Twist1) 52 . However, according to the expression of α-SMA these cells correspond with myofibroblasts, which possess cellular plasticity and multipotency 53 .…”

Section: Cells Involved In Epithelial Carcinogenesismentioning

confidence: 99%

From Molecular Biology to Epithelial Carcinogenesis

Méndez¹

2021

Preprint

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The theory of the origin of carcinomas suggests that neoplasias from epithelial tissues are the consequence of the reactivation of developmental programs. It proposes a model in which the epithelial cells undergo cellular transitions due to replicative senescence and inflammation towards a mesenchymal-undifferentiated phenotype with cancerous behavior. The conserved pattern of histological progression and the molecular biology of carcinomas is congruent with the view of cancer as a developmental disease. In support of the theory, the experimental literature regarding the molecular, cellular, and histopathological mechanisms associated with epithelial carcinogenesis were aligned according to the premises of the hypothesis. Thereby identified a generic process in the carcinogenesis of the breast, endometrium, prostate, colon, lung, pancreas, bladder, liver, and cervix. Then, is provided a methodology overview of modeling in systems biology derived from previous research testing the hypothesis. The results illustrate the value of the complex systems approach to recover behavior that cannot be inferred only by traditional methods. Specifically, the model suggests that the consistency in the cell types and the directionality of the observed cellular transitions during epithelial carcinogenesis arise from structural constraints in the molecular networks associated with the carcinomas. Overall, the results of the dynamical analysis agree with the premises of the hypothesis and provide an insightful perspective of the potential mechanisms underlying the cellular plasticity displayed during epithelial carcinogenesis. In an era of big data and yet few advances in the underlying causes of chronic diseases, the manuscript also aims to inspire molecular biologists to integrate existing empirical evidence with systems biology modeling in the pursuit of understanding.

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Section: Cells Involved In Epithelial Carcinogenesismentioning

confidence: 99%

From Molecular Biology to Epithelial Carcinogenesis

Méndez¹

2021

Preprint

View full text Add to dashboard Cite

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On the Origin of Carcinoma

Méndez¹

2021

Preprint

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The origin of cancer remains one of the most important enigmas in modern biology. The prevailing paradigm has failed to grasp a comprehensive view of the disease. Naturally, therapies developed under the current assumptions are inadequate and cancer is practically an incurable disease. Meanwhile, descriptive studies continuously extend the molecular complexity of cancer without an equivalent advancement in its understanding. Furthermore, they tend to accumulate inconsistencies inexplicable under the classical view. This paper presents a compelling theory of the origin of carcinomas. By hypothesis, a series of generic events in epithelial tissues promoted by cellular aging and inflammation enables the reactivation of developmental programs. The origin of carcinomas in vivo is described as the time-ordered cell state transitions undergone by epithelial cells in the hyperplasia due to replicative senescence and inflammation towards a mesenchymal undifferentiated endogenous cell state with cancerous behavior. In support of the theory, the molecular, cellular, and histopathological evidence is critically reviewed. A plausible model for the origin of carcinomas is presented to explain the mechanism underlying carcinogenesis from an evolutive and developmental perspective. The implications of the hypothesis in the current strategies for cancer prevention and treatment are discussed along with rational alternatives and some predictions for possible experimental validation.

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Gatekeeper transcription factors regulate switch between lineage preservation and cell plasticity

Cited by 2 publications

References 27 publications

From Molecular Biology to Epithelial Carcinogenesis

From Molecular Biology to Epithelial Carcinogenesis

On the Origin of Carcinoma

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