The Experts below are selected from a list of 468 Experts worldwide ranked by ideXlab platform
Chengchao Shou - One of the best experts on this subject based on the ideXlab platform.
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Extracellular Gamma-Synuclein promotes tumor cell motility by activating β1 integrin-focal adhesion kinase signaling pathway and increasing matrix metalloproteinase-24, -2 protein secretion.
Journal of Experimental & Clinical Cancer Research, 2018Co-Authors: Like Qu, Chuanke Zhao, Chengchao ShouAbstract:Increasing evidence reveals a significant correlation between Gamma-Synuclein (SNCG) level and tumor invasion and metastasis in various human cancers. Our previous investigation showed that SNCG could secrete into extracellular environment and promoted tumor cell motility, but the mechanism is unknown. The membrane binding ability of SNCG was characterized by immunohistochemical staining, immunofluorescence staining and fractionation of colorectal cancer (CRC) cell membrane. Association between SNCG and β1 integrin was validated by coimmunoprecipitation and far Western blot. After inhibition of β1 integrin and focal adhesion kinase (FAK), effect of SNCG on cell motility was measured by transwell chamber assays and changes of protein levels were detected by Western blot. Association between SNCG and activated β1 integrin levels in human CRC tissues was determined by Spearman’s rank correlation analysis. Secreted proteins in conditioned medium (CM) were screened by antibody array. Extracellular SNCG bound β1 integrin on CRC cell membrane and increased levels of activated β1 integrin and FAK. Correspondingly, SNCG-enhanced cell motility was counteracted by knockdown or inhibition of β1 integrin or FAK. Further study revealed that high SNCG level indicated poor outcome and SNCG levels positively correlated with those of activated β1 integrin and phospho-FAK (Tyr397) in human CRC tissues. Additionally, extracellular SNCG promoted secretion of fibronectin (FN), vitronectin (VN), matrix metalloproteinase (MMP)-2, and MMP-24 from HCT116 cells. Protease activity of MMP-2 in the CM of HCT116 cells was increased by treatment with SNCG, which was abolished by inhibiting β1 integrin. Our results highlight the potential role of SNCG in remodeling extracellular microenvironment and inducing β1 integrin-FAK signal pathway of CRC cells.
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Extracellular Gamma-Synuclein promotes tumor cell motility by activating β1 integrin-focal adhesion kinase signaling pathway and increasing matrix metalloproteinase-24, -2 protein secretion
'Springer Science and Business Media LLC', 2018Co-Authors: Caiyun Liu, Chuanke Zhao, Chengchao ShouAbstract:Abstract Background Increasing evidence reveals a significant correlation between Gamma-Synuclein (SNCG) level and tumor invasion and metastasis in various human cancers. Our previous investigation showed that SNCG could secrete into extracellular environment and promoted tumor cell motility, but the mechanism is unknown. Methods The membrane binding ability of SNCG was characterized by immunohistochemical staining, immunofluorescence staining and fractionation of colorectal cancer (CRC) cell membrane. Association between SNCG and β1 integrin was validated by coimmunoprecipitation and far Western blot. After inhibition of β1 integrin and focal adhesion kinase (FAK), effect of SNCG on cell motility was measured by transwell chamber assays and changes of protein levels were detected by Western blot. Association between SNCG and activated β1 integrin levels in human CRC tissues was determined by Spearman’s rank correlation analysis. Secreted proteins in conditioned medium (CM) were screened by antibody array. Results Extracellular SNCG bound β1 integrin on CRC cell membrane and increased levels of activated β1 integrin and FAK. Correspondingly, SNCG-enhanced cell motility was counteracted by knockdown or inhibition of β1 integrin or FAK. Further study revealed that high SNCG level indicated poor outcome and SNCG levels positively correlated with those of activated β1 integrin and phospho-FAK (Tyr397) in human CRC tissues. Additionally, extracellular SNCG promoted secretion of fibronectin (FN), vitronectin (VN), matrix metalloproteinase (MMP)-2, and MMP-24 from HCT116 cells. Protease activity of MMP-2 in the CM of HCT116 cells was increased by treatment with SNCG, which was abolished by inhibiting β1 integrin. Conclusion Our results highlight the potential role of SNCG in remodeling extracellular microenvironment and inducing β1 integrin-FAK signal pathway of CRC cells
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urine Gamma Synuclein as a biomarker for the diagnosis of bladder cancer
Oncotarget, 2016Co-Authors: Caiyun Liu, Bingbing Shi, Chonghua Hao, Qinghai Wang, Nianzeng Xing, Jianzhong Shou, Yanning Gao, Chao Qin, Jiyu Zhao, Chengchao ShouAbstract:Gamma-Synuclein (SNCG) is secreted from tumor cells and elevated in the urine of bladder cancer (BCa) patients, however, the diagnostic and prognostic values of urine SNCG for BCa remain unknown. Here, we used enzyme immunoassay and western blotting to measure urine SNCG levels. Patients with BCa or other urological diseases and healthy controls were enrolled at four Chinese hospitals from April 2010 to November 2014. Diagnostic performance was evaluated by analyzing the area under receiver operating characteristic curves (AUROCs). The AUROC was 0.903 ± 0.019 (95% confidence interval [CI], 0.867 - 0.940) for the test and 0.929 ± 0.015 (95% CI, 0.901 - 0.958) for the validation cohort. The optimal cutoff value yielded sensitivities of 68.4%, 62.4% and specificities of 97.4%, 97.8% for the test and validation cohort, respectively. Urine SNCG levels were decreased after tumor resection, but were higher in BCa patients with recurrence than those without (P = 0.001). The urine SNCG levels in patients with urological benign diseases were significantly lower than BCa patients (all P < 0.05) but higher than healthy controls (all P < 0.05). Hematuria did not interfere with the SNCG detection by spiking urine specimens with whole blood. Compared with a nuclear-matrix-protein-22 assay in an additional cohort excluding hematuria, SNCG showed a similar sensitivity and higher specificity. In summary, our results demonstrated that urine SNCG can discriminate BCa from urinary diseases, and is a useful prognosticator of postsurgical recurrence.
John Q. Trojanowski - One of the best experts on this subject based on the ideXlab platform.
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alzheimer s pathology in human temporal cortex surgically excised after severe brain injury
Experimental Neurology, 2004Co-Authors: Milos D Ikonomovic, Kunihiro Uryu, John Q. Trojanowski, Eric E Abrahamson, John R Ciallella, Robert S B Clark, Donald W Marion, Stephen R Wisniewski, Steven T DekoskyAbstract:Traumatic brain injury (TBI) is a risk factor for the development of Alzheimer's disease (AD). This immunohistochemical study determined the extent of AD-related changes in temporal cortex resected from individuals treated surgically for severe TBI. Antisera generated against Abeta species (total Abeta, Abeta(1-42), and Abeta(1-40)), the C-terminal of the Abeta precursor protein (APP), apolipoprotein E (apoE), and markers of neuron structure and degeneration (tau, ubiquitin, alpha-, beta-, and Gamma-Synuclein) were used to examine the extent of Abeta plaque deposition and neurodegenerative changes in 18 TBI subjects (ages 18-64 years). Diffuse cortical Abeta deposits were observed in one third of subjects (aged 35-62 years) as early as 2 h after injury, with only one (35-year old) individual exhibiting "mature", dense-cored plaques. Plaque-like deposits, neurons, glia, and axonal changes were also immunostained with APP and apoE antibodies. In plaque-positive cases, the only statistically significant change in cellular immunostaining was increased neuronal APP (P = 0.013). There was no significant correlation between the distribution of Abeta plaques and markers of neuronal degeneration. Diffuse tau immunostaining was localized to neuronal cell soma, axons or glial cells in a larger subset of individuals. Tau-positive, neurofibrillary tangle (NFT)-like changes were detected in only two subjects, both of more advanced age and who were without Abeta deposits. Other neurodegenerative changes, evidenced by ubiquitin- and Synuclein-immunoreactive neurons, were abundant in the majority of cases. Our results demonstrate a differential distribution and course of intra- and extra-cellular AD-like changes during the acute phase following severe TBI in humans. Abeta plaques and early evidence of neuronal degenerative changes can develop rapidly after TBI, while fully developed NFTs most likely result from more chronic disease- or injury-related processes. These observations lend further support to the hypothesis that head trauma significantly increases the risk of developing pathological and clinical symptoms of AD, and provide insight into the molecular mechanisms that initiate these pathological cascades very early during severe brain injury.
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expression of alpha beta and Gamma Synuclein in glial tumors and medulloblastomas
Acta Neuropathologica, 2003Co-Authors: Kar Ming Fung, Virginia M.-y. Lee, Lucy B Rorke, Benoit I Giasson, John Q. TrojanowskiAbstract:alpha-, beta- and Gamma-Synuclein are highly homologous proteins that are found predominantly in neurons. Abnormal accumulation of Synucleins has been associated with diseases of the central nervous system particularly Parkinson's disease. Immunoreactivity of alpha-Synuclein is demonstrated in brain tumors with neuronal differentiation and in schwannomas, whereas Gamma-Synuclein has been demonstrated in breast and ovarian carcinomas. The immunoreactivity of Synucleins has not been described in glial tumors. Immunoreactivity of Synucleins in glial cells in culture and in pathological conditions, however, suggests that Synucleins may be expressed by glial tumors. We studied the expression of alpha-, beta-, and Gamma-Synuclein in 84 human brain tumors (24 ependymomas, 31 astrocytomas, 8 oligodendrogliomas, and 21 medulloblastomas) by immunohistochemistry. Our study demonstrates immunoreactivity for Gamma-Synuclein in high-grade glial tumors; immunoreactivity is found in all anaplastic ependymomas but in only 33% of ependymomas and 16% of myxopapillary ependymomas. Immunoreactivity for Gamma-Synuclein is noted in 63% of glioblastomas but not in other astrocytic tumors. Of medulloblastomas, 76% have immunoreactivity for either alpha- or beta-Synuclein or both; no immunoreactivity for Gamma-Synuclein is seen in medulloblastomas.
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Synucleins are developmentally expressed, and alpha-Synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2000Co-Authors: Diane D. Murphy, John Q. Trojanowski, Susan M. Rueter, Virginia M.-y. LeeAbstract:alpha-, beta-, and Gamma-Synuclein, a novel family of neuronal proteins, has become the focus of research interest because alpha-Synuclein has been increasingly implicated in the pathogenesis of Parkinson's and Alzheimer's disease. However, the normal functions of the Synucleins are still unknown. For this reason, we characterized alpha-, beta-, and Gamma-Synuclein expression in primary hippocampal neuronal cultures and showed that the onset of alpha- and beta-Synuclein expression was delayed after synaptic development, suggesting that these Synucleins may not be essential for synapse formation. In mature cultured primary neurons, alpha- and beta-Synuclein colocalized almost exclusively with synaptophysin in the presynaptic terminal, whereas little Gamma-Synuclein was expressed at all. To assess the function of alpha-Synuclein, we suppressed expression of this protein with antisense oligonucleotide technology. Morphometric ultrastructural analysis of the alpha-Synuclein antisense oligonucleotide-treated cultures revealed a significant reduction in the distal pool of synaptic vesicles. These data suggest that one function of alpha-Synuclein may be to regulate the size of distinct pools of synaptic vesicles in mature neurons.
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the expression of α β and γ Synucleins in olfactory mucosa from patients with and without neurodegenerative diseases
Experimental Neurology, 1999Co-Authors: John E Duda, Virginia M.-y. Lee, Usman Shah, Steven E Arnold, John Q. TrojanowskiAbstract:A family of homologous proteins known as alpha-, beta-, and Gamma-Synuclein are abundantly expressed in brain, especially in the presynaptic terminal of neurons. Although the precise function of these proteins remains unknown, alpha-Synuclein has been implicated in synaptic plasticity associated with avian song learning as well as in the pathogenesis of Parkinson's disease (PD), dementia with LBs (DLB), some forms of Alzheimer's disease (AD), and multiple system atrophy (MSA). Since olfactory dysfunction is a common feature of these disorders and the olfactory receptor neurons (ORNs) of the olfactory epithelium (OE) regenerate throughout the lifespan, we used antibodies specific for alpha-, beta-, and Gamma-Synucleins to examine the olfactory mucosa of patients with PD, DLB, AD, MSA, and controls without a neurological disorder. Although antibodies to alpha- and beta-Synucleins detected abnormal dystrophic neurites in the OE of patients with neurodegenerative disorders, similar pathology was also seen in the OE of controls. More significantly, we show here for the first time that alpha-, beta-, and Gamma-Synucleins are differentially expressed in cells of the OE and respiratory epithelium and that alpha-Synuclein is the most abundant Synuclein in the olfactory mucosa, where it is prominently expressed in ORNs. Moreover, alpha- and Gamma-Synucleins also were prominent in the OE basal cells, which include the progenitor cells of the ORNs in the OE. Thus, our data on Synuclein expression within the OE may signify that Synuclein plays a role in the regeneration and plasticity of ORNs in the adult human OE.
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Axon pathology in Parkinson's disease and Lewy body dementia hippocampus contains alpha-, beta-, and Gamma-Synuclein.
Proceedings of the National Academy of Sciences of the United States of America, 1999Co-Authors: James E. Galvin, Kunihiro Uryu, John Q. TrojanowskiAbstract:Pathogenic α-Synuclein (αS) gene mutations occur in rare familial Parkinson’s disease (PD) kindreds, and wild-type αS is a major component of Lewy bodies (LBs) in sporadic PD, dementia with LBs (DLB), and the LB variant of Alzheimer’s disease, but β-Synuclein (βS) and γ-Synuclein (γS) have not yet been implicated in neurological disorders. Here we show that in PD and DLB, but not normal brains, antibodies to αS and βS reveal novel presynaptic axon terminal pathology in the hippocampal dentate, hilar, and CA2/3 regions, whereas antibodies to γS detect previously unrecognized axonal spheroid-like lesions in the hippocampal dentate molecular layer. The aggregation of other synaptic proteins and synaptic vesicle-like structures in the αS- and βS-labeled hilar dystrophic neurites suggests that synaptic dysfunction may result from these lesions. Our findings broaden the concept of neurodegenerative “Synucleinopathies” by implicating βS and γS, in addition to αS, in the onset/progression of PD and DLB.
Yangfu Jiang - One of the best experts on this subject based on the ideXlab platform.
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Gamma Synuclein is a novel Twist1 target that promotes TGF-β-induced cancer cell migration and invasion.
Cell Death and Disease, 2018Co-Authors: Ting Shao, Peiying Song, Qingbin Kong, Jiao Wang, Hongying Zhang, Yangfu JiangAbstract:Transforming growth factor β (TGF-β) is critical for embryonic development, adult tissue homeostasis, and tumor progression. TGF-β suppresses tumors at early stage, but promotes metastasis at later stage through oncogenes such as Twist1. Gamma-Synuclein (SNCG) is overexpressed in a variety of invasive and metastatic cancer. Here, we show that TGF-β induces SNCG expression by Smad-Twist1 axis, thus promoting TGF-β- and Twist1-induced cancer cell migration and invasion. We identify multiple Twist1-binding sites (E-boxes) in SNCG promoter. Chromatin immunoprecipitation and luciferase assays confirm the binding of Twist1 to the E-boxes of SNCG promoter sequence (−129/−1026 bp). Importantly, the Twist1-binding site close to the transcription initiation site is critical for the upregulation of SNCG expression by TGF-β and Twist1. Mutations of Twist1 motif on the SNCG promoter constructs markedly reduces the promoter activity. We further show that TGF-β induces Twist1 expression through Smad thereby enhancing the binding of Twist1 to SNCG promoter, upregulating SNCG promoter activity and increasing SNCG expression. SNCG knockdown abrogates TGF-β- or Twist1-induced cancer cell migration and invasion. Finally, SNCG knockdown inhibits the promotion of cancer metastasis by Twist1. Together, our data demonstrate that SNCG is a novel target of TGF-β-Smad-Twist1 axis and a mediator of Twist1-induced cancer metastasis.
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Up-regulation of Gamma-Synuclein contributes to cancer cell survival under endoplasmic reticulum stress.
The Journal of pathology, 2008Co-Authors: Hui Hua, Jiao Wang, Jing Jing, Ting Luo, Yangfu JiangAbstract:Previous studies have demonstrated that Gamma-Synuclein is overexpressed in a variety of human malignancies. Overexpression of Gamma-Synuclein in human breast cancer cells leads to an increase in cell motility, resistance to chemotherapeutic drugs, and mitotic checkpoint dysfunction. We report in this study that Gamma-Synuclein is up-regulated by endoplasmic reticulum stress. The up-regulation of Gamma-Synuclein expression by endoplasmic reticulum stress is mediated, at least in part, by activation transcription factor (ATF) 4. Knockdown of Gamma-Synuclein sensitized human breast cancer cells to endoplasmic reticulum stress-induced apoptosis. Induction of apoptosis by endoplasmic reticulum stress when Gamma-Synuclein was inhibited was dependent on JNK or caspase activation, with caspase-3 and caspase-7 being involved. Treatment with the JNK or caspase-3 and caspase-7 inhibitor partially blocked endoplasmic reticulum stress-induced apoptosis in breast cancer cells transfected with or without the siRNA against Gamma-Synuclein. Taken together, these data suggest that Gamma-Synuclein may promote cancer progression by suppressing endoplasmic reticulum stress-induced apoptosis.
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stage specific expression of breast cancer specific gene Gamma Synuclein
Cancer Epidemiology Biomarkers & Prevention, 2003Co-Authors: Ziyi Weng, Yangfu Jiang, Qinghua Tao, Gufa Lin, Huiqin Qian, Yichu Zhang, Xiaoyan Ding, Yuenian Eric ShiAbstract:γ-Synuclein (SNCG), also referred as breast cancer-specific gene 1, is the third member of a neuronal protein family Synuclein. SNCG is highly expressed in human-infiltrating breast carcinomas but not expressed in normal or benign breast tissues. To evaluate the clinical relevance of SNCG expression in breast cancer progression and its correlation with clinical parameters, we analyzed SNCG expression in 79 clinical breast specimens from primary breast cancer, hyperplasia, and fibroadenoma patients by reverse transcription-PCR. The status of estrogen receptor, progesterone receptor, proliferating cell nuclear antigen, and C-erBb2 was also analyzed by immunohistochemistry. Overall SNCG mRNA expression was detectable in 38.8% of breast cancers. However, 79% of stage III/IV breast cancers were positive for SNCG expression, whereas only 15% of stage I/II breast cancers were positive for SNCG expression. In contrast, the expression of SNCG was undetectable in all benign breast lesions. The expression of SNCG was strongly correlated to the stage of breast cancer (P = 0.000). This study suggests that the expression of SNCG is stage specific for breast cancer. SNCG is expected to be a useful marker for breast cancer progression and a potential target for breast cancer treatment.
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neural protein Synuclein Gamma sncg in breast cancer progression
2002Co-Authors: Yangfu JiangAbstract:Abstract : Synucleins are emerging as a central player in the fundamental neural processes and in the formation of pathologically insoluble deposits characteristic of Alzheimer's (AD) and Parkinson's (PD) diseases. However, the normal cellular function of this highly conserved Synuclein family remains largely unknown. Using differential cDNA sequencing approach, we first identified a breast cancer specific gene, BCSG1, which was expressed abundantly in metastatic breast cancer cDNA library but scarcely in normal breast cDNA library. Interestingly, BCSG1 revealed no homology to any other known growth factors or oncogenes; rather, BCSG1 revealed extensive sequence homology to neurotic proteins of alpha Synuclein and beta Synuclein, and thus was also named as Gamma Synuclein (SNCG). SNCG expression is highly associated with breast cancer and ovarian cancer progression. In addition, overexpression of SNCG in breast cancer cells significantly stimulated cell growth in vitro and tumor metastasis in vivo. However, the molecular targets of SNCG aberrant expression for breast cancer have not been identified. For the first time, we report a chaperone-like activity of SNCG in stimulating the transcriptional activity of estrogen receptor-alpha(ER-alpha) in breast cancer cells. Consistent with the stimulation of ER-alpha, SNCG stimulated the ligand-dependent cell proliferation. While overexpresssion of SNCG stimulated the ligand-dependent cell proliferation, suppression of endogenous SNCG expression significantly inhibited cell growth in response to estrogen. The stimulatory effect of SNCG on ERalpha-regulated gene expression and cell growth can be effectively inhibited by antiestrogens. Demonstration of the stimulation of ER-alpha signaling as one of the cellular functions of SNCG will have a great impact on the biology of steroid receptors and the pathological role of SNCG on hormone-responsive tumors including breast, ovary, and prostate.
Like Qu - One of the best experts on this subject based on the ideXlab platform.
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Extracellular Gamma-Synuclein promotes tumor cell motility by activating β1 integrin-focal adhesion kinase signaling pathway and increasing matrix metalloproteinase-24, -2 protein secretion.
Journal of Experimental & Clinical Cancer Research, 2018Co-Authors: Like Qu, Chuanke Zhao, Chengchao ShouAbstract:Increasing evidence reveals a significant correlation between Gamma-Synuclein (SNCG) level and tumor invasion and metastasis in various human cancers. Our previous investigation showed that SNCG could secrete into extracellular environment and promoted tumor cell motility, but the mechanism is unknown. The membrane binding ability of SNCG was characterized by immunohistochemical staining, immunofluorescence staining and fractionation of colorectal cancer (CRC) cell membrane. Association between SNCG and β1 integrin was validated by coimmunoprecipitation and far Western blot. After inhibition of β1 integrin and focal adhesion kinase (FAK), effect of SNCG on cell motility was measured by transwell chamber assays and changes of protein levels were detected by Western blot. Association between SNCG and activated β1 integrin levels in human CRC tissues was determined by Spearman’s rank correlation analysis. Secreted proteins in conditioned medium (CM) were screened by antibody array. Extracellular SNCG bound β1 integrin on CRC cell membrane and increased levels of activated β1 integrin and FAK. Correspondingly, SNCG-enhanced cell motility was counteracted by knockdown or inhibition of β1 integrin or FAK. Further study revealed that high SNCG level indicated poor outcome and SNCG levels positively correlated with those of activated β1 integrin and phospho-FAK (Tyr397) in human CRC tissues. Additionally, extracellular SNCG promoted secretion of fibronectin (FN), vitronectin (VN), matrix metalloproteinase (MMP)-2, and MMP-24 from HCT116 cells. Protease activity of MMP-2 in the CM of HCT116 cells was increased by treatment with SNCG, which was abolished by inhibiting β1 integrin. Our results highlight the potential role of SNCG in remodeling extracellular microenvironment and inducing β1 integrin-FAK signal pathway of CRC cells.
Caiyun Liu - One of the best experts on this subject based on the ideXlab platform.
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Extracellular Gamma-Synuclein promotes tumor cell motility by activating β1 integrin-focal adhesion kinase signaling pathway and increasing matrix metalloproteinase-24, -2 protein secretion
'Springer Science and Business Media LLC', 2018Co-Authors: Caiyun Liu, Chuanke Zhao, Chengchao ShouAbstract:Abstract Background Increasing evidence reveals a significant correlation between Gamma-Synuclein (SNCG) level and tumor invasion and metastasis in various human cancers. Our previous investigation showed that SNCG could secrete into extracellular environment and promoted tumor cell motility, but the mechanism is unknown. Methods The membrane binding ability of SNCG was characterized by immunohistochemical staining, immunofluorescence staining and fractionation of colorectal cancer (CRC) cell membrane. Association between SNCG and β1 integrin was validated by coimmunoprecipitation and far Western blot. After inhibition of β1 integrin and focal adhesion kinase (FAK), effect of SNCG on cell motility was measured by transwell chamber assays and changes of protein levels were detected by Western blot. Association between SNCG and activated β1 integrin levels in human CRC tissues was determined by Spearman’s rank correlation analysis. Secreted proteins in conditioned medium (CM) were screened by antibody array. Results Extracellular SNCG bound β1 integrin on CRC cell membrane and increased levels of activated β1 integrin and FAK. Correspondingly, SNCG-enhanced cell motility was counteracted by knockdown or inhibition of β1 integrin or FAK. Further study revealed that high SNCG level indicated poor outcome and SNCG levels positively correlated with those of activated β1 integrin and phospho-FAK (Tyr397) in human CRC tissues. Additionally, extracellular SNCG promoted secretion of fibronectin (FN), vitronectin (VN), matrix metalloproteinase (MMP)-2, and MMP-24 from HCT116 cells. Protease activity of MMP-2 in the CM of HCT116 cells was increased by treatment with SNCG, which was abolished by inhibiting β1 integrin. Conclusion Our results highlight the potential role of SNCG in remodeling extracellular microenvironment and inducing β1 integrin-FAK signal pathway of CRC cells
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urine Gamma Synuclein as a biomarker for the diagnosis of bladder cancer
Oncotarget, 2016Co-Authors: Caiyun Liu, Bingbing Shi, Chonghua Hao, Qinghai Wang, Nianzeng Xing, Jianzhong Shou, Yanning Gao, Chao Qin, Jiyu Zhao, Chengchao ShouAbstract:Gamma-Synuclein (SNCG) is secreted from tumor cells and elevated in the urine of bladder cancer (BCa) patients, however, the diagnostic and prognostic values of urine SNCG for BCa remain unknown. Here, we used enzyme immunoassay and western blotting to measure urine SNCG levels. Patients with BCa or other urological diseases and healthy controls were enrolled at four Chinese hospitals from April 2010 to November 2014. Diagnostic performance was evaluated by analyzing the area under receiver operating characteristic curves (AUROCs). The AUROC was 0.903 ± 0.019 (95% confidence interval [CI], 0.867 - 0.940) for the test and 0.929 ± 0.015 (95% CI, 0.901 - 0.958) for the validation cohort. The optimal cutoff value yielded sensitivities of 68.4%, 62.4% and specificities of 97.4%, 97.8% for the test and validation cohort, respectively. Urine SNCG levels were decreased after tumor resection, but were higher in BCa patients with recurrence than those without (P = 0.001). The urine SNCG levels in patients with urological benign diseases were significantly lower than BCa patients (all P < 0.05) but higher than healthy controls (all P < 0.05). Hematuria did not interfere with the SNCG detection by spiking urine specimens with whole blood. Compared with a nuclear-matrix-protein-22 assay in an additional cohort excluding hematuria, SNCG showed a similar sensitivity and higher specificity. In summary, our results demonstrated that urine SNCG can discriminate BCa from urinary diseases, and is a useful prognosticator of postsurgical recurrence.
