The Experts below are selected from a list of 18723 Experts worldwide ranked by ideXlab platform
Chung-hsing Chen - One of the best experts on this subject based on the ideXlab platform.
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Wild-type p53 upregulates an early onset breast cancer-associated gene GAS7 to suppress metastasis via GAS7–CYFIP1-mediated signaling pathway
Oncogene, 2018Co-Authors: Jer-wei Chang, Wen-hung Kuo, Chiao-mei Lin, Wen-ling Chen, Shih-hsuan Chan, Meng-fan Chiu, I-shou Chang, Shih-sheng Jiang, Fang-yu Tsai, Chung-hsing ChenAbstract:The early onset breast cancer patients (age ≤ 40) often display higher incidence of axillary lymph node metastasis, and poorer five-year survival than the late-onset patients. To identify the genes and molecules associated with poor prognosis of early onset breast cancer, we examined gene expression profiles from paired breast normal/tumor tissues, and coupled with Gene Ontology and public data base analysis. Our data showed that the expression of GAS7b gene was lower in the early onset breast cancer patients as compared to the elder patients. We found that GAS7 was associated with CYFIP1 and WAVE2 complex to suppress breast cancer metastasis via blocking CYFIP1 and Rac1 Protein interaction, actin polymerization, and β1-integrin/FAK/Src signaling. We further demonstrated that p53 directly regulated GAS7 gene expression, which was inversely correlated with p53 mutations in breast cancer specimens. Our study uncover a novel regulatory mechanism of p53 in early onset breast cancer progression through GAS7–CYFIP1-mediated signaling pathways.
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Wild-type p53 upregulates an early onset breast cancer-associated gene GAS7 to suppress metastasis via GAS7-CYFIP1-mediated signaling pathway.
Oncogene, 2018Co-Authors: Jer-wei Chang, Wen-hung Kuo, Chiao-mei Lin, Wen-ling Chen, Shih-hsuan Chan, Meng-fan Chiu, I-shou Chang, Shih-sheng Jiang, Fang-yu Tsai, Chung-hsing ChenAbstract:The early onset breast cancer patients (age ≤ 40) often display higher incidence of axillary lymph node metastasis, and poorer five-year survival than the late-onset patients. To identify the genes and molecules associated with poor prognosis of early onset breast cancer, we examined gene expression profiles from paired breast normal/tumor tissues, and coupled with Gene Ontology and public data base analysis. Our data showed that the expression of GAS7b gene was lower in the early onset breast cancer patients as compared to the elder patients. We found that GAS7 was associated with CYFIP1 and WAVE2 complex to suppress breast cancer metastasis via blocking CYFIP1 and Rac1 Protein interaction, actin polymerization, and β1-integrin/FAK/Src signaling. We further demonstrated that p53 directly regulated GAS7 gene expression, which was inversely correlated with p53 mutations in breast cancer specimens. Our study uncover a novel regulatory mechanism of p53 in early onset breast cancer progression through GAS7–CYFIP1-mediated signaling pathways.
Anders Arner - One of the best experts on this subject based on the ideXlab platform.
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The small GTPase Rac1 is required for smooth muscle contraction
The Journal of Physiology, 2013Co-Authors: Awahan Rahman, Benjamin Davis, Cecilia Lövdahl, Veena T. Hanumaiah, Cord Brakebusch, Robert Feil, Anders ArnerAbstract:The role of the small GTP-binding Protein Rac1 in smooth muscle contraction was examined using small molecule inhibitors (EHT1864, NSC23766) and a novel smooth muscle-specific, conditional, Rac1 knockout mouse strain. EHT1864, which affects nucleotide binding and inhibits Rac1 activity, concentration-dependently inhibited the contractile responses induced by several different modes of activation (high-K+, phenylephrine, carbachol and Protein kinase C activation by phorbol-12,13-dibutyrate) in several different visceral (urinary bladder, ileum) and vascular (mesenteric artery, saphenous artery, aorta) smooth muscle tissues. This contractile inhibition was associated with inhibition of the Ca2+ transient. Knockout of Rac1 (with a 50% loss of Rac1 Protein) lowered active stress in the urinary bladder and the saphenous artery consistent with a role of Rac1 in facilitating smooth muscle contraction. NSC23766, which blocks interaction between Rac1 and some guanine nucleotide exchange factors, specifically inhibited the α1 receptor responses (phenylephrine) in vascular tissues and potentiated prostaglandin F2α and thromboxane (U46619) receptor responses. The latter potentiating effect occurred at lowered intracellular [Ca2+]. These results show that Rac1 activity is required for active contraction in smooth muscle, probably via enabling an adequate Ca2+ transient. At the same time, specific agonists recruit Rac1 signalling via upstream modulators, resulting in either a potentiation of contraction via Ca2+ mobilization (α1 receptor stimulation) or an attenuated contraction via inhibition of Ca2+ sensitization (prostaglandin and thromboxane receptors).
Jer-wei Chang - One of the best experts on this subject based on the ideXlab platform.
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Wild-type p53 upregulates an early onset breast cancer-associated gene GAS7 to suppress metastasis via GAS7–CYFIP1-mediated signaling pathway
Oncogene, 2018Co-Authors: Jer-wei Chang, Wen-hung Kuo, Chiao-mei Lin, Wen-ling Chen, Shih-hsuan Chan, Meng-fan Chiu, I-shou Chang, Shih-sheng Jiang, Fang-yu Tsai, Chung-hsing ChenAbstract:The early onset breast cancer patients (age ≤ 40) often display higher incidence of axillary lymph node metastasis, and poorer five-year survival than the late-onset patients. To identify the genes and molecules associated with poor prognosis of early onset breast cancer, we examined gene expression profiles from paired breast normal/tumor tissues, and coupled with Gene Ontology and public data base analysis. Our data showed that the expression of GAS7b gene was lower in the early onset breast cancer patients as compared to the elder patients. We found that GAS7 was associated with CYFIP1 and WAVE2 complex to suppress breast cancer metastasis via blocking CYFIP1 and Rac1 Protein interaction, actin polymerization, and β1-integrin/FAK/Src signaling. We further demonstrated that p53 directly regulated GAS7 gene expression, which was inversely correlated with p53 mutations in breast cancer specimens. Our study uncover a novel regulatory mechanism of p53 in early onset breast cancer progression through GAS7–CYFIP1-mediated signaling pathways.
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Wild-type p53 upregulates an early onset breast cancer-associated gene GAS7 to suppress metastasis via GAS7-CYFIP1-mediated signaling pathway.
Oncogene, 2018Co-Authors: Jer-wei Chang, Wen-hung Kuo, Chiao-mei Lin, Wen-ling Chen, Shih-hsuan Chan, Meng-fan Chiu, I-shou Chang, Shih-sheng Jiang, Fang-yu Tsai, Chung-hsing ChenAbstract:The early onset breast cancer patients (age ≤ 40) often display higher incidence of axillary lymph node metastasis, and poorer five-year survival than the late-onset patients. To identify the genes and molecules associated with poor prognosis of early onset breast cancer, we examined gene expression profiles from paired breast normal/tumor tissues, and coupled with Gene Ontology and public data base analysis. Our data showed that the expression of GAS7b gene was lower in the early onset breast cancer patients as compared to the elder patients. We found that GAS7 was associated with CYFIP1 and WAVE2 complex to suppress breast cancer metastasis via blocking CYFIP1 and Rac1 Protein interaction, actin polymerization, and β1-integrin/FAK/Src signaling. We further demonstrated that p53 directly regulated GAS7 gene expression, which was inversely correlated with p53 mutations in breast cancer specimens. Our study uncover a novel regulatory mechanism of p53 in early onset breast cancer progression through GAS7–CYFIP1-mediated signaling pathways.
José L. Zugaza - One of the best experts on this subject based on the ideXlab platform.
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Rac1 Protein Regulates Glycogen Phosphorylase Activation and Controls Interleukin (IL)-2-dependent T Cell Proliferation
The Journal of biological chemistry, 2012Co-Authors: Onetsine Arrizabalaga, Hadriano M. Lacerda, Ana M. Zubiaga, José L. ZugazaAbstract:Small GTPases of the Rho family have been implicated in important cellular processes such as cell migration and adhesion, Protein secretion, and/or gene transcription. In the lymphoid system, these GTPases participate in the signaling cascades that are activated after engagement of antigen receptors. However, little is known about the role that Rho GTPases play in IL-2-mediated responses. Here, we show that IL-2 induces Rac1 activation in Kit 225 T cells. We identified by mass spectrometry the muscle isoform of glycogen phosphorylase (PYGM) as a novel Rac1 effector molecule in IL-2-stimulated cells. The interaction between the active form of Rac1 (Rac1-GTP) and PYGM was established directly through a domain comprising amino acids 191–270 of PYGM that exhibits significant homology with the Rac binding domain of PAK1. The integrity of this region was crucial for PYGM activation. Importantly, IL-2-dependent cellular proliferation was inhibited upon blocking both the activation of Rac1 and the activity of PYGM. These results reveal a new role for Rac1 in cell signaling, showing that this GTPase triggers T cell proliferation upon IL-2 stimulation by associating with PYGM and modulating its enzymatic activity.
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Rac1 Protein Regulates Glycogen Phosphorylase Activation and Controls Interleukin (IL)-2-dependent T Cell
2012Co-Authors: Onetsine Arrizabalaga, Hadriano M. Lacerda, Ana M. Zubiaga, José L. Zugaza, Fromthe ‡ DepartmentofgeneticsAbstract:Small GTPases of the Rho family have been implicated in important cellular processes such as cell migration and adhesion, Protein secretion, and/or gene transcription. In the lymphoid system, these GTPases participate in the signaling cascades that are activated after engagement of antigen receptors. However, little is known about the role that Rho GTPases play in IL-2-mediated responses. Here, we show that IL-2 induces Rac1 activation in Kit 225 T cells. We identified by mass spectrometry the muscle isoform of glycogen phosphorylase (PYGM) as a novel Rac1 effector molecule in IL-2-stimulated cells. The interaction between the active form of Rac1 (Rac1-GTP) and PYGM was established directly through a domain comprising amino acids 191–270 of PYGM that exhibits significant homology with the Rac binding domain of PAK1. The integrity of this region was crucial for PYGM activation. Importantly, IL-2-dependent cellular proliferation was inhibited upon blocking both the activation of Rac1 and the activity of PYGM. These results reveal a new role for Rac1 in cell signaling, showing that this GTPase triggers T cell proliferation upon IL-2 stimulation by associating with PYGM and modulating its enzymatic activity.
Nik Muller - One of the best experts on this subject based on the ideXlab platform.
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Topical Application of Tat-Rac1 Promotes Cutaneous Wound Healing in Normal and Diabetic Mice.
International journal of biological sciences, 2018Co-Authors: Bin Fan, Tao Wang, Li Bian, Zhe Jian, Dongyan D. Wang, Tao Bai, Gongyi Zhang, Nik MullerAbstract:The endogenous small GTPase, Rac1, plays a critical role during normal skin wound healing. It remains to be determined whether endogenous Rac1 can be appropriately activated in chronic wounds; if not, whether exogenous Rac1 has therapeutic effects on wound healing. Here we show that Rac1 Protein levels were lower in wounds of db/db diabetic mice than wounds in wild type mice during the healing process. To assess the therapeutic potential of exogenous Rac1 in wound healing, we produced a Tat-Rac1 fusion Protein that enters into cells through Protein transduction. Tat-Rac1 increased proliferation and migration of keratinocytes and dermal fibroblasts in vitro. Topical application of Tat-Rac1 accelerated cutaneous wound closure in vivo in db/db mice as well as wild type mice. Further analyses revealed that Tat-Rac1 had faster re-epithelialization, higher keratinocyte proliferation and migration without an earlier onset of myofibroblast activation than vehicle treated wounds. Tat-Rac1 also reduced inflammation in wounds. Our findings revealed the failure of diabetic wounds to elevate Rac1 expression and suggested a therapeutic strategy utilizing a Rac1-based biologic to compensate for this defect thereby promoting wound healing.
