Lateral Inhibition in Cell Specification Mediated by Mechanical Signals Modulating TAZ Activity

Xia, Peng; Gütl, Daniel J; Zheden, Vanessa; Heisenberg, Carl‐Philipp

doi:10.1016/j.cell.2019.01.019

Cited by 50 publications

(40 citation statements)

References 43 publications

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“…Numerous studies have reported that the PI3K/AKT pathway plays an important role in metastasis through the regulation of EMT [23][24][25]. Therefore, the PI3K inhibitor LY294002 [26][27][28][29] was used to detect the effect of the PI3K/AKT pathway on AGK-induced RCC proliferation and metastasis. As shown in Fig.…”

Section: Agk Promotes Rcc Proliferation and Metastasis Via The Pi3k/amentioning

confidence: 99%

Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3β signalling pathway in renal cell carcinoma

Zhu

Zhong

et al. 2020

J Hematol Oncol

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Background: Clinically, the median survival in patients with metastatic renal cell carcinoma (RCC) was only 6-12 months and a 5-year survival rate of less than 20%. Therefore, an in-depth study of the molecular mechanisms involved in RCC is of great significance for improving the survival of patients with advanced RCC. Acylglycerol kinase (AGK) is a newly discovered lipid kinase that has been reported to be a potent oncogene that may be involved in the regulation of malignant progression in a variety of tumours. However, the expression and biological characteristics of the AGK gene in RCC remain unclear. Methods: AGK expression was quantified by quantitative real-time PCR, Western blotting and immunohistochemistry in RCC cell lines and paired patient tissues. Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of AGK in human RCC tissue samples. Chi-squared test was performed to analyse the correlation between AGK expression and the clinicopathological features. Stable overexpression and knockdown of AGK in RCC cells was constructed with lentivirus. The oncogenic effects of AGK in human RCC progression were investigated using assays of colony formation, anchorage-independent growth, EdU assay, cell cycle analysis, wound-healing, trans-well analysis and xenograft tumour model. GSEA and KEGG analysis were conducted to detect the potential pathway of AGK involved in RCC. These results were further confirmed using the luciferase reporter assays, immunofluorescence and in vivo experiments. Results: AGK expression is significantly elevated in RCC and closely related to the malignant development and poor prognosis in RCC patients. By in vitro and in vivo experiments, AGK was shown to enhance the proliferation of RCC cells by promoting the transition from the G1 phase to the S phase in the cell cycle and to enhance the migration and invasion by promoting epithelial-mesenchymal transition. By activating the PI3K/AKT/GSK3β signalling pathway in RCC, AGK can increase nuclear accumulation of β-catenin, which further upregulated TCF/LEF transcription factor activity. Conclusions: AGK promotes the progression of RCC via activating the PI3K/AKT/GSK3β signalling pathway and might be a potential target for the further research of RCC.

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Section: Agk Promotes Rcc Proliferation and Metastasis Via The Pi3k/amentioning

confidence: 99%

Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3β signalling pathway in renal cell carcinoma

Zhu

Zhong

et al. 2020

J Hematol Oncol

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“…Such growth factor-mediated lateral inhibition can explain the salt-and-pepper distribution of cell types in the ICM (Chazaud et al, 2006;Rossant et al, 2003), although cell movement within the ICM likely precludes the observation of the canonical, alternate distribution of fates. Besides Delta-Notch signaling, lateral inhibition can also result from mechanical cues (Xia et al, 2019) and from secreted signaling molecules (Thompson et al, 2004). It has been proposed that high local concentrations of FGF4 may underlie this stochastic distribution of fates in the ICM of the blastocyst (Bessonnard et al, 2014;Kang et al, 2017;Tosenberger et al, 2017) and that the identity of neighbor cells affects fate choice (Fischer et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Growth-factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development

Saiz

Mora-Bitria

Rahman

et al. 2020

eLife

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Precise control and maintenance of population size is fundamental for organismal development and homeostasis. The three cell types of the mammalian blastocyst are generated in precise proportions over a short time, suggesting a mechanism to ensure a reproducible outcome. We developed a minimal mathematical model demonstrating growth factor signaling is sufficient to guarantee this robustness and which anticipates an embryo's response to perturbations in lineage composition. Addition of lineage-restricted cells both in vivo and in silico, causes a shift of the fate of progenitors away from the supernumerary cell type, while eliminating cells using laser ablation biases the specification of progenitors towards the targeted cell type. Finally, FGF4 couples fate decisions to lineage composition through changes in local growth factor concentration, providing a basis for the regulative abilities of the early mammalian embryo whereby fate decisions are coordinated at the population level to robustly generate tissues in the right proportions.

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“…Such growth factor-mediated lateral inhibition can explain the salt-and-pepper distribution of cell types in the ICM (Chazaud et al, 2006;Rossant et al, 2003), although cell movement within the ICM likely precludes the observation of the canonical, alternate distribution of fates. Besides Delta-Notch signaling, lateral inhibition can also result from mechanical cues (Xia et al, 2019) and from secreted signaling molecules (Thompson et al, 2004). It has been proposed that high local concentrations of FGF4 may underlie this stochastic distribution of fates in the ICM of the blastocyst (Bessonnard et al, 2014;Kang et al, 2013;Tosenberger et al, 2017) and that the identity of neighbor cells affects fate choice (Fischer et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Growth factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development

Saiz

Mora-Bitria

Rahman

et al. 2019

Preprint

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Precise control and maintenance of the size of cell populations is fundamental for organismal development and homeostasis. The three cell types that comprise the mammalian blastocyststage embryo are generated in precise proportions and over a short time, suggesting a size control mechanism ensures a reproducible outcome. Guided by experimental observations, we developed a minimal mathematical model that shows growth factor signaling is sufficient to guarantee this robustness. The model anticipates, without additional parameter fitting, the response of the embryo to perturbations in its lineage composition. We experimentally added lineage-restricted cells to the epiblast both in vivo and in silico, which resulted in a shift of the fate of progenitors away from the supernumerary cell type, while eliminating cells using laser ablation biased the specification of progenitors towards the targeted cell type. Finally, we show that FGF4 couples cell fate decisions to lineage composition through changes in local concentration of the growth factor. Our results provide a basis for the regulative abilities of the mammalian embryo and reveal how, in a self-organizing system, individual cell fate decisions are coordinated at the population level to robustly generate tissues in the right proportions.

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Lateral Inhibition in Cell Specification Mediated by Mechanical Signals Modulating TAZ Activity

Cited by 50 publications

References 43 publications

Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3β signalling pathway in renal cell carcinoma

Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3β signalling pathway in renal cell carcinoma

Growth-factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development

Growth factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development

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