Microtubule acetylation but not detyrosination promotes focal adhesion dynamics and cell migration

Bance, Bertille; Seetharaman, Shailaja; Leduc, Cécile; Boëda, Batiste; Etienne-Manneville, Sandrine

doi:10.1101/425421

Cited by 3 publications

(2 citation statements)

References 47 publications

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“…The drugs contained in GSF can regulate insulin resistance and the PPAR signaling pathway; improve the utilization of lipids and sugars by the body through specific effects on INS, PPARG, ADIPOQ, and other targets (especially fat metabolism regulated by insulin); and improve the efficiency of utilization of sugars and lipids (Feige et al, 2006;Frühbeck et al, 2014). GSF can also regulate and inhibit changes in the cytoskeleton, reduce the migration of glial cells, improve vascular endothelial function (Bance et al, 2019;Natale et al, 2019), inhibit processes that damage podocytes, protect nephrons, and improve the symptoms of kidney damage in the M2 community by interfering with VEGFA, PRKCB, and JNK in the focal adhesion pathway.…”

Section: Discussionmentioning

confidence: 99%

Effect of botanical drugs in improving symptoms of hypertensive nephropathy: Analysis of real-world data, retrospective cohort, network, and experimental assessment

Huan

et al. 2023

Front. Pharmacol.

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Background/aim: Hypertensive nephropathy (HN) is a common complication of hypertension. Traditional Chinese medicine has long been used in the clinical treatment of Hypertensive nephropathy. However, botanical drug prescriptions have not been summarized. The purpose of this study is to develop a prescription for improving hypertensive nephropathy, explore the evidence related to clinical application of the prescription, and verify its molecular mechanism of action.Methods: In this study, based on the electronic medical record data on Hypertensive nephropathy, the core botanical drugs and patients’ symptoms were mined using the hierarchical network extraction and fast unfolding algorithm, and the protein interaction network between botanical drugs and Hypertensive nephropathy was established. The K-nearest neighbors (KNN) model was used to analyze the clinical and biological characteristics of botanical drug compounds to determine the effective compounds. Hierarchical clustering was used to screen for effective botanical drugs. The clinical efficacy of botanical drugs was verified by a retrospective cohort. Animal experiments were performed at the target and pathway levels to analyze the mechanism.Results: A total of 14 botanical drugs and five symptom communities were obtained from real-world clinical data. In total, 76 effective compounds were obtained using the K-nearest neighbors model, and seven botanical drugs were identified as Gao Shen Formula by hierarchical clustering. Compared with the classical model, the Area under the curve (AUC) value of the K-nearest neighbors model was the best; retrospective cohort verification showed that Gao Shen Formula reduced serum creatinine levels and Chronic kidney disease (CKD) stage [OR = 2.561, 95% CI (1.025–6.406), p < 0.05]. With respect to target and pathway enrichment, Gao Shen Formula acts on inflammatory factors such as TNF-α, IL-1β, and IL-6 and regulates the NF-κB signaling pathway and downstream glucose and lipid metabolic pathways.Conclusion: In the retrospective cohort, we observed that the clinical application of Gao Shen Formula alleviates the decrease in renal function in patients with hypertensive nephropathy. It is speculated that Gao Shen Formula acts by reducing inflammatory reactions, inhibiting renal damage caused by excessive activation of the renin-angiotensin-aldosterone system, and regulating energy metabolism.

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Section: Discussionmentioning

confidence: 99%

Effect of botanical drugs in improving symptoms of hypertensive nephropathy: Analysis of real-world data, retrospective cohort, network, and experimental assessment

Huan

et al. 2023

Front. Pharmacol.

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“…Microtubule acetylation is controlled by the cytoplasmic deacetylase Histone deacetylase 6 (HDAC6). HDAC6 promotes oncogene-induced cell transformation, cell motility and metastasis (Lee et al, 2008;Lafarga et al, 2012;Bance et al, 2019). For example, it is required for the proliferation and metastasis of melanoma cells (Stivarou et al, 2016;Hu et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

Regulation of cellular contractile force, shape and migration of fibroblasts by oncogenes and Histone deacetylase 6

López-Guajardo,

Zafar,

Al Hennawi

et al. 2023

Front. Mol. Biosci.

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The capacity of cells to adhere to, exert forces upon and migrate through their surrounding environment governs tissue regeneration and cancer metastasis. The role of the physical contractile forces that cells exert in this process, and the underlying molecular mechanisms are not fully understood. We, therefore, aimed to clarify if the extracellular forces that cells exert on their environment and/or the intracellular forces that deform the cell nucleus, and the link between these forces, are defective in transformed and invasive fibroblasts, and to indicate the underlying molecular mechanism of control. Confocal, Epifluorescence and Traction force microscopy, followed by computational analysis, showed an increased maximum contractile force that cells apply on their environment and a decreased intracellular force on the cell nucleus in the invasive fibroblasts, as compared to normal control cells. Loss of HDAC6 activity by tubacin-treatment and siRNA-mediated HDAC6 knockdown also reversed the reduced size and more circular shape and defective migration of the transformed and invasive cells to normal. However, only tubacin-mediated, and not siRNA knockdown reversed the increased force of the invasive cells on their surrounding environment to normal, with no effects on nuclear forces. We observed that the forces on the environment and the nucleus were weakly positively correlated, with the exception of HDAC6 siRNA-treated cells, in which the correlation was weakly negative. The transformed and invasive fibroblasts showed an increased number and smaller cell-matrix adhesions than control, and neither tubacin-treatment, nor HDAC6 knockdown reversed this phenotype to normal, but instead increased it further. This highlights the possibility that the control of contractile force requires separate functions of HDAC6, than the control of cell adhesions, spreading and shape. These data are consistent with the possibility that defective force-transduction from the extracellular environment to the nucleus contributes to metastasis, via a mechanism that depends upon HDAC6. To our knowledge, our findings present the first correlation between the cellular forces that deforms the surrounding environment and the nucleus in fibroblasts, and it expands our understanding of how cells generate contractile forces that contribute to cell invasion and metastasisis.

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Meeting report – Building the Cell 2018

Bertin

Lomakin

2019

Journal of Cell Science

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Cell biologists from all around the world gathered in Paris on the 26 to 28 September 2018 to participate in the 3rd international meeting 'Building the Cell'. It was organized by Heĺeǹe Barelli, Arnaud Echard, Thierry Galli, Florence Niedergang, Manuel Theŕy and Marie Heĺeǹe Verlhac on behalf of the French Society for Cell Biology (SBCF) at the Institut Pasteur. Around 230 participants joined the meeting for stimulating talks, discussions, poster sessions, and a gala dinner on the Seine that included a music performance by the rock group 'Membrane Band'. The unifying theme of the meeting was the development of creative multidisciplinary approaches to understand cellular life at different scales in a dynamic and quantitative manner. Here, we summarize the results presented at the meeting and the emerging ideas from the different sessions.The 3rd international meeting 'Building the Cell' (Fig. 1; Fig. 2) was divided into ten different sessions that covered a variety of topics including intracellular trafficking, cell division, cytoskeletal dynamics and cell mechanics, cancer and stem cell biology, embryonic development and tissue morphogenesis, neurobiology, and aggregates and phase transitions. A broad spectrum of modern approaches and experimental systems ranging from synthetic biology and stem cell technologies to 3D organoids and animal models was presented. The meeting highlighted some of the latest and novel findings in cell biology, often coupled to major methodological developments in quantitative microscopy and computational modelling, as well as cell and tissue micro-engineering.Membrane, intracellular trafficking and mechanics

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Microtubule acetylation but not detyrosination promotes focal adhesion dynamics and cell migration

Cited by 3 publications

References 47 publications

Effect of botanical drugs in improving symptoms of hypertensive nephropathy: Analysis of real-world data, retrospective cohort, network, and experimental assessment

Effect of botanical drugs in improving symptoms of hypertensive nephropathy: Analysis of real-world data, retrospective cohort, network, and experimental assessment

Regulation of cellular contractile force, shape and migration of fibroblasts by oncogenes and Histone deacetylase 6

Meeting report – Building the Cell 2018

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