The Experts below are selected from a list of 3213 Experts worldwide ranked by ideXlab platform
Nguan Soon Tan - One of the best experts on this subject based on the ideXlab platform.
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Nuclear receptor peroxisome proliferator activated receptor (PPAR) β/δ in skin wound healing and cancer
European Journal of Dermatology, 2015Co-Authors: Alexandra Montagner, Walter Wahli, Nguan Soon TanAbstract:We review the functions of peroxisome proliferator activated receptor (PPAR) β/δ in skin wound healing and cancer. In particular, we highlight the roles of PPARβ/δ in inhibiting keratinocyte apoptosis at wound edges via activation of the PI3K/PKBα/Akt1 pathway and its role during re-epithelialization in regulating keratinocyte adhesion and migration. In fibroblasts, PPARβ/δ controls IL-1 signalling and thereby contributes to the homeostatic control of keratinocyte proliferation. We discuss its therapeutic potential for treating diabetic wounds and inflammatory skin diseases such as psoriasis and acne vulgaris. PPARβ/δ is classified as a tumour growth modifier; it is activated by chronic low-grade inflammation, which promotes the production of lipids that, in turn, enhance PPARβ/δ transcription activity. Our earlier work unveiled a cascade of events triggered by PPAR-/- that involve the Oncogene Src, which promotes ultraviolet-induced skin cancer in mice via enhanced EGFR/Erk1/2 signalling and the expression of epithelial-to-mesenchymal transition (EMT) markers. Interestingly, PPARβ/δ expression is correlated with the expression of Src and EMT markers in human skin squamous cell carcinoma. Furthermore, there is a positive interaction between PPARβ/δ, Src, and TGF-1 at the transcriptional level in various human epithelial cancers. Taken together, these observations suggest the need for evaluating PPARβ/δ modulators that attenuate or increase its activity, depending on the therapeutic target.
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Nuclear receptor peroxisome proliferator activated receptor (PPAR) beta/delta in skin wound healing and cancer
European Journal of Dermatology, 2015Co-Authors: Alexandra Montagner, Walter Wahli, Nguan Soon TanAbstract:We review the functions of peroxisome proliferator activated receptor (PPAR) beta/delta in skin wound healing and cancer. In particular, we highlight the roles of PPAR beta/delta in inhibiting keratinocyte apoptosis at wound edges via activation of the PI3K/PKB alpha/Akt1 pathway and its role during re-epithelialization in regulating keratinocyte adhesion and migration. In fibroblasts, PPAR beta/delta controls IL-1 signalling and thereby contributes to the homeostatic control of keratinocyte proliferation. We discuss its therapeutic potential for treating diabetic wounds and inflammatory skin diseases such as psoriasis and acne vulgaris. PPAR beta/delta is classified as a tumour growth modifier; it is activated by chronic low-grade inflammation, which promotes the production of lipids that, in turn, enhance PPAR beta/delta transcription activity. Our earlier,work unveiled a cascade of events triggered by PPAR beta/delta that involve the Oncogene Src, which promotes ultraviolet-induced skin cancer in mice via enhanced EGFR/Erk1/2 signalling and the expression of epithelial-to-mesenchymal transition (EMT) markers. Interestingly, PPAR beta/delta expression is correlated with the expression of Src and EMT markers in human skin squamous cell carcinoma. Furthermore, there is a positive interaction between PPAR beta/delta, Src, and TGF beta 1 at the transcriptional level in various human epithelial cancers. Taken together, these observations suggest the need for evaluating PPAR beta/delta modulators that attenuate or increase its activity, depending on the therapeutic target.
Greg J Beitel - One of the best experts on this subject based on the ideXlab platform.
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Drosophila Src regulates anisotropic apical surface growth to control epithelial tube size
Nature Cell Biology, 2012Co-Authors: Kevin S. Nelson, József Mihály, Imre Molnar, Matthias Kaschube, Zia Khan, Greg J BeitelAbstract:Beitel and colleagues show that the proto-Oncogene Src regulates tracheal tube dimensions in Drosophila by directing anisotropic apical membrane growth in concert with the formin dDaam.AbstractNetworks of epithelial and endothelial tubes are essential for the function of organs such as the lung, kidney and vascular system. The sizes and shapes of these tubes are highly regulated to match their individual functions. Defects in tube size can cause debilitating diseases such as polycystic kidney disease and ischaemia^ 1 , 2 . It is therefore critical to understand how tube dimensions are regulated. Here we identify the tyrosine kinase Src as an instructive regulator of epithelial-tube length in the Drosophila tracheal system. Loss-of-function Src42 mutations shorten tracheal tubes, whereas Src42 overexpression elongates them. Surprisingly, Src42 acts distinctly from known tube-size pathways and regulates both the amount of apical surface growth and, with the conserved formin dDaam, the direction of growth. Quantitative three-dimensional image analysis reveals that Src42 - and dDaam -mutant tracheal cells expand more in the circumferential than the axial dimension, resulting in tubes that are shorter in length—but larger in diameter—than wild-type tubes. Thus, Src42 and dDaam control tube dimensions by regulating the direction of anisotropic growth, a mechanism that has not previously been described.
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Drosophila Src regulates anisotropic apical surface growth to control epithelial tube size
Nature Cell Biology, 2012Co-Authors: Kevin S. Nelson, József Mihály, Imre Molnar, Matthias Kaschube, Zia Khan, Greg J BeitelAbstract:Beitel and colleagues show that the proto-Oncogene Src regulates tracheal tube dimensions in Drosophila by directing anisotropic apical membrane growth in concert with the formin dDaam.
Alexandra Montagner - One of the best experts on this subject based on the ideXlab platform.
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Nuclear receptor peroxisome proliferator activated receptor (PPAR) β/δ in skin wound healing and cancer
European Journal of Dermatology, 2015Co-Authors: Alexandra Montagner, Walter Wahli, Nguan Soon TanAbstract:We review the functions of peroxisome proliferator activated receptor (PPAR) β/δ in skin wound healing and cancer. In particular, we highlight the roles of PPARβ/δ in inhibiting keratinocyte apoptosis at wound edges via activation of the PI3K/PKBα/Akt1 pathway and its role during re-epithelialization in regulating keratinocyte adhesion and migration. In fibroblasts, PPARβ/δ controls IL-1 signalling and thereby contributes to the homeostatic control of keratinocyte proliferation. We discuss its therapeutic potential for treating diabetic wounds and inflammatory skin diseases such as psoriasis and acne vulgaris. PPARβ/δ is classified as a tumour growth modifier; it is activated by chronic low-grade inflammation, which promotes the production of lipids that, in turn, enhance PPARβ/δ transcription activity. Our earlier work unveiled a cascade of events triggered by PPAR-/- that involve the Oncogene Src, which promotes ultraviolet-induced skin cancer in mice via enhanced EGFR/Erk1/2 signalling and the expression of epithelial-to-mesenchymal transition (EMT) markers. Interestingly, PPARβ/δ expression is correlated with the expression of Src and EMT markers in human skin squamous cell carcinoma. Furthermore, there is a positive interaction between PPARβ/δ, Src, and TGF-1 at the transcriptional level in various human epithelial cancers. Taken together, these observations suggest the need for evaluating PPARβ/δ modulators that attenuate or increase its activity, depending on the therapeutic target.
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Nuclear receptor peroxisome proliferator activated receptor (PPAR) beta/delta in skin wound healing and cancer
European Journal of Dermatology, 2015Co-Authors: Alexandra Montagner, Walter Wahli, Nguan Soon TanAbstract:We review the functions of peroxisome proliferator activated receptor (PPAR) beta/delta in skin wound healing and cancer. In particular, we highlight the roles of PPAR beta/delta in inhibiting keratinocyte apoptosis at wound edges via activation of the PI3K/PKB alpha/Akt1 pathway and its role during re-epithelialization in regulating keratinocyte adhesion and migration. In fibroblasts, PPAR beta/delta controls IL-1 signalling and thereby contributes to the homeostatic control of keratinocyte proliferation. We discuss its therapeutic potential for treating diabetic wounds and inflammatory skin diseases such as psoriasis and acne vulgaris. PPAR beta/delta is classified as a tumour growth modifier; it is activated by chronic low-grade inflammation, which promotes the production of lipids that, in turn, enhance PPAR beta/delta transcription activity. Our earlier,work unveiled a cascade of events triggered by PPAR beta/delta that involve the Oncogene Src, which promotes ultraviolet-induced skin cancer in mice via enhanced EGFR/Erk1/2 signalling and the expression of epithelial-to-mesenchymal transition (EMT) markers. Interestingly, PPAR beta/delta expression is correlated with the expression of Src and EMT markers in human skin squamous cell carcinoma. Furthermore, there is a positive interaction between PPAR beta/delta, Src, and TGF beta 1 at the transcriptional level in various human epithelial cancers. Taken together, these observations suggest the need for evaluating PPAR beta/delta modulators that attenuate or increase its activity, depending on the therapeutic target.
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Src Is Activated by the Nuclear Receptor Peroxisome Proliferator-Activated Receptor β/δ in Ultraviolet Radiation-Induced Skin Cancer
Embo Molecular Medicine, 2013Co-Authors: Alexandra Montagner, Maria Belen Delgado, Corinne Tallichet-blanc, Jeremy Soon Kiat Chan, Ming K. Sng, Hélène Mottaz, Gwendoline Degueurce, Yannick Lippi, Catherine Moret, Michaël BaruchetAbstract:Although non-melanoma skin cancer (NMSC) is the most common human cancer and its incidence continues to rise worldwide, the mechanisms underlying its development remain incompletely understood. Here, we unveil a cascade of events involving peroxisome proliferator-activated receptor (PPAR) β/δ and the Oncogene Src, which promotes the development of ultraviolet (UV)-induced skin cancer in mice. UV-induced PPARβ/δ activity, which directly stimulated Src expression, increased Src kinase activity and enhanced the EGFR/Erk1/2 signalling pathway, resulting in increased epithelial-to-mesenchymal transition (EMT) marker expression. Consistent with these observations, PPARβ/δ-null mice developed fewer and smaller skin tumours, and a PPARβ/δ antagonist prevented UV-dependent Src stimulation. Furthermore, the expression of PPARβ/δ positively correlated with the expression of Src and EMT markers in human skin squamous cell carcinoma (SCC), and critically, linear models applied to several human epithelial cancers revealed an interaction between PPARβ/δ and Src and TGFβ1 transcriptional levels. Taken together, these observations motivate the future evaluation of PPARβ/δ modulators to attenuate the development of several epithelial cancers.
Kevin S. Nelson - One of the best experts on this subject based on the ideXlab platform.
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Drosophila Src regulates anisotropic apical surface growth to control epithelial tube size
Nature Cell Biology, 2012Co-Authors: Kevin S. Nelson, József Mihály, Imre Molnar, Matthias Kaschube, Zia Khan, Greg J BeitelAbstract:Beitel and colleagues show that the proto-Oncogene Src regulates tracheal tube dimensions in Drosophila by directing anisotropic apical membrane growth in concert with the formin dDaam.AbstractNetworks of epithelial and endothelial tubes are essential for the function of organs such as the lung, kidney and vascular system. The sizes and shapes of these tubes are highly regulated to match their individual functions. Defects in tube size can cause debilitating diseases such as polycystic kidney disease and ischaemia^ 1 , 2 . It is therefore critical to understand how tube dimensions are regulated. Here we identify the tyrosine kinase Src as an instructive regulator of epithelial-tube length in the Drosophila tracheal system. Loss-of-function Src42 mutations shorten tracheal tubes, whereas Src42 overexpression elongates them. Surprisingly, Src42 acts distinctly from known tube-size pathways and regulates both the amount of apical surface growth and, with the conserved formin dDaam, the direction of growth. Quantitative three-dimensional image analysis reveals that Src42 - and dDaam -mutant tracheal cells expand more in the circumferential than the axial dimension, resulting in tubes that are shorter in length—but larger in diameter—than wild-type tubes. Thus, Src42 and dDaam control tube dimensions by regulating the direction of anisotropic growth, a mechanism that has not previously been described.
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Drosophila Src regulates anisotropic apical surface growth to control epithelial tube size
Nature Cell Biology, 2012Co-Authors: Kevin S. Nelson, József Mihály, Imre Molnar, Matthias Kaschube, Zia Khan, Greg J BeitelAbstract:Beitel and colleagues show that the proto-Oncogene Src regulates tracheal tube dimensions in Drosophila by directing anisotropic apical membrane growth in concert with the formin dDaam.
Ruth Birnergruenberger - One of the best experts on this subject based on the ideXlab platform.
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deletion of adipose triglyceride lipase links triacylglycerol accumulation to a more aggressive phenotype in a549 lung carcinoma cells
Journal of Proteome Research, 2018Co-Authors: Tamara Tomin, Katarina Fritz, Juergen Gindlhuber, Linda Waldherr, Bettina Pucher, Gerhard G Thallinger, Daniel K Nomura, Matthias Schittmayer, Ruth BirnergruenbergerAbstract:Adipose triglyceride lipase (ATGL) catalyzes the rate limiting step in triacylglycerol breakdown in adipocytes but is expressed in most tissues. The enzyme was shown to be lost in many human tumors, and its loss may play a role in early stages of cancer development. Here, we report that loss of ATGL supports a more-aggressive cancer phenotype in a model system in which ATGL was deleted in A549 lung cancer cells by CRISPR/Cas9. We observed that loss of ATGL led to triacylglycerol accumulation in lipid droplets and higher levels of cellular phospholipid and bioactive lipid species (lyso- and ether-phospholipids). Label-free quantitative proteomics revealed elevated expression of the pro-Oncogene Src kinase in ATGL depleted cells, which was also found on mRNA level and confirmed on protein level by Western blot. Consistently, higher expression of phosphorylated (active) Src (Y416 phospho-Src) was observed in ATGL-KO cells. Cells depleted of ATGL migrated faster, which was dependent on Src kinase activity. We...
