Robustness of epithelial sealing is an emerging property of local ERK feedback driven by cell elimination

Valon, Léo; Davidović, Anđela; Levillayer, Florence; Villars, Alexis; Chouly, Mathilde; Cerqueira-Campos, Fabiana; Levayer, Romain

doi:10.1016/j.devcel.2021.05.006

Cited by 84 publications

(83 citation statements)

References 38 publications

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“…Another key question is how biochemical signaling, including mitogenic signaling, that emerges from the apoptotic process, contributes to compensatory proliferation. It has been shown recently that extracellular-signal-regulated kinase (ERK) is activated in most of the neighboring cells upon apoptosis and acts as a survival factor for these cells [32,33]. Our data support the idea that mitogenic signals secreted from the apoptotic cell are crucial as demonstrated before [5–11], but not solely sufficient, to explain the spatially inhomogeneous nature of compensatory proliferation.…”

Section: Discussionsupporting

confidence: 89%

Mechanics defines the spatial pattern of compensatory proliferation

Kawaue

Yow

et al. 2021

Preprint

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The number of cells in tissues is tightly controlled by cell division and cell death, and misregulation of cell numbers could lead to pathological conditions such as cancer. To maintain cell numbers in a tissue, a cell elimination process named programmed cell death or apoptosis, stimulates the proliferation of neighboring cells. This mechanism is called apoptosis-induced compensatory proliferation, which was originally reported more than 40 years ago. While only a limited number of the neigboring cells need to divide to compensate for apoptotic cell loss, the mechanisms that select cells for undergoing division remain an open question. Here we found that the spatial inhomogeneity in mechanotransduction through a growth-promoting transcription co-activator Yes-associated protein (YAP) in the neighboring tissue, accounts for the inhomogeneity of compensatory proliferation. Such inhomogeneous mechanotransduction arises from the combination of the non-uniform distribution of nuclear size, which is inherent in tissues, and the non-uniform pattern of mechanical force applied to the neighboring cells upon apoptosis. Our findings from a mechanical perspective complement the current biochemical understanding of compensatory growth and provide additional insights into cellular functions of how tissue precisely maintains its homeostasis.

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Section: Discussionsupporting

confidence: 89%

Mechanics defines the spatial pattern of compensatory proliferation

Kawaue

Yow

et al. 2021

Preprint

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“…However, if endothelial cells only rely on local replication function, it is far from enough to resist external damage 63 . A recently study shows that the protection is driven by a transient activation of extracellular-signal-regulated kinase (ERK) in endothelial cells neighboring extruding cells, which inhibits caspase activation and prevents elimination of endothelial cells in clusters 64 . Endothelial progenitor cells (EPCs) in the circulation participate in another repairing mechanism for maintaining the integrity of the endothelium, which has been clearly explained 65 .…”

Section: Endothelial Cell Functionsmentioning

confidence: 99%

Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function

et al. 2021

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As a first-line treatment for diabetes, the insulin-sensitizing biguanide, metformin, regulates glucose levels and positively affects cardiovascular function in patients with diabetes and cardiovascular complications. Endothelial dysfunction (ED) represents the primary pathological change of multiple vascular diseases, because it causes decreased arterial plasticity, increased vascular resistance, reduced tissue perfusion and atherosclerosis. Caused by “biochemical injury”, ED is also an independent predictor of cardiovascular events. Accumulating evidence shows that metformin improves ED through liver kinase B1 (LKB1)/5'-adenosine monophosphat-activated protein kinase (AMPK) and AMPK-independent targets, including nuclear factor-kappa B (NF-κB), phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), endothelial nitric oxide synthase (eNOS), sirtuin 1 (SIRT1), forkhead box O1 (FOXO1), krüppel-like factor 4 (KLF4) and krüppel-like factor 2 (KLF2). Evaluating the effects of metformin on endothelial cell functions would facilitate our understanding of the therapeutic potential of metformin in cardiovascular diabetology (including diabetes and its cardiovascular complications). This article reviews the physiological and pathological functions of endothelial cells and the intact endothelium, reviews the latest research of metformin in the treatment of diabetes and related cardiovascular complications, and focuses on the mechanism of action of metformin in regulating endothelial cell functions.

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“…Another lead for explaining the survival of border untransformed cells could be the generation of ERK waves. Indeed, it has been shown recently that ectopic induction of apoptosis in epithelia composed of wt cells triggers ERK waves in the surrounding non-dying cells, which supports survival through inhibition of caspases [112]. Therefore, it is plausible that a similar mechanism takes place in the surrounding wt cells of a scrib −/− dying tumor.…”

Section: Scrib −/− Model-a Tumor Suppressive Role Of the Microenvironment Through Cell Competitionmentioning

confidence: 99%

RasV12; scrib−/− Tumors: A Cooperative Oncogenesis Model Fueled by Tumor/Host Interactions

Dillard

Reis

Rusten

2021

IJMS

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The phenomenon of how oncogenes and tumor-suppressor mutations can synergize to promote tumor fitness and cancer progression can be studied in relatively simple animal model systems such as Drosophila melanogaster. Almost two decades after the landmark discovery of cooperative oncogenesis between oncogenic RasV12 and the loss of the tumor suppressor scribble in flies, this and other tumor models have provided new concepts and findings in cancer biology that has remarkable parallels and relevance to human cancer. Here we review findings using the RasV12; scrib−/− tumor model and how it has contributed to our understanding of how these initial simple genetic insults cooperate within the tumor cell to set in motion the malignant transformation program leading to tumor growth through cell growth, cell survival and proliferation, dismantling of cell–cell interactions, degradation of basement membrane and spreading to other organs. Recent findings have demonstrated that cooperativity goes beyond cell intrinsic mechanisms as the tumor interacts with the immediate cells of the microenvironment, the immune system and systemic organs to eventually facilitate malignant progression.

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Robustness of epithelial sealing is an emerging property of local ERK feedback driven by cell elimination

Cited by 84 publications

References 38 publications

Mechanics defines the spatial pattern of compensatory proliferation

Mechanics defines the spatial pattern of compensatory proliferation

Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function

RasV12; scrib−/− Tumors: A Cooperative Oncogenesis Model Fueled by Tumor/Host Interactions

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